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• CAD cells are a useful model for studies of APP cell biology and Alzheimers disease pathology, including Aβ accumulation within neurites.    0 Comment(s)
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• Description:

  This hypothesis describes the use of CAD cells as a model system to study the cell biology of APP, including its metabolism, intracellular transport, function, and implication in neuronal degeneration. CAD cells express the neuronal form of APP (APP695), a fraction of which is transported within neurites at velocities similar to those reported for cultured hippocampal neurons. Like in neurons, in CAD cells, APP is processed by secretase activities to generate sAPPs, Aβ, and CTFs - including the AICD (part of which is translocated into the nucleus). Both the full-length APP and the CTFs become phosphorylated – via multiple signaling pathways - at a critical threonine residue in the cytoplasmic domain (Thr668 in APP695). Aβ is produced intracellularly in CAD cells, and forms low- and high-number oligomers that occasionally accumulate at neurite terminals. Thus, an essential feature of the neuronal pathology thought to occur in Alzheimer’s disease can be reproduced – and studied - in CAD cells.

• Authors: Muresan Z  Muresan V 
• Part of:
  • Brainstem neurons are initiators of neuritic plaques. (Muresan et al., 2008)

• Muresan, Zoia

  Muresan, Virgil

• Contains 10 Statements:
  10 with evidence   0 without evidence   and a total of: 70 citations ;   Related to external statements: 1 consistent    0 inconsistent   0 discussed   0 with alternatives  
  a b c d
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  1. CAD (Cath.a-differentiated) cells, a mouse neuronal cell line, which originates in the locus coeruleus in the brainstem, have neuronal phenotype when differentiated, with characteristics of catecholaminergic neurons.

     SHOW Details   Supporting(17)     Genes/Proteins: (1)

     Description: CAD cells are normal diploid, chromosomally stable cells. Like PC12 cells, CAD cells can be grown in an undifferentiated state (doubling time 18-22 hours). Differentiation is induced by serum removal, when cells stop dividing, grow processes, and switch to an autocrine survival mode. CAD cells express neuronal markers, maintain active signaling pathways characteristic for catecholaminergic neurons, and possess ion channels, transporters, and synaptic proteins. CAD cells express several dopamine receptor subtypes, and possess the biosynthetic machinery that produces L-DOPA. GFAP, a glia-specific cytoskeletal protein, is not detected in CAD cells by Western blotting, although immunocytochemistry studies suggest that CAD cells may express low levels of GFAP. Initially established by targeted oncogenesis in mice, CAD cells have spontaneously lost the original oncogene, SV40 T antigen. Ultrastructurally, their processes resemble true neurites that contain dense-core and clear vesicles. Electrophysiological experiments indicate that they behave like fully functional neurons. Thus, CAD cells are faithful to brain biology.
     Experimental Approach: Animal models,   Biomarkers
     Pathogenic Narrative Tags: Perturbation
     Supporting Evidence
     

     • Suri C, Fung B, Tischler A, Chikaraishi D
       Catecholaminergic cell lines from the brain and adrenal glands of tyrosine hydroxylase-SV40 T antigen transgenic mice.
       The Journal of neuroscience : the official journal of the Society for Neuroscience. 1993 Mar;13(3):1280-91
     • Donai H, Nakamura M, Sogawa Y, Wang J, Urushihara M, Yamauchi T
       Involvement of Ca2+/calmodulin-dependent protein kinase II in neurite outgrowth induced by cAMP treatment and serum deprivation in a central nervous system cell line, CAD derived from rat brain.
       Neuroscience letters. 2000 Oct 27;293(2):111-4
     • Li Y, Hou L, Aktiv A, Dahlström A
       Immunohistochemical characterisation of differentiated CAD cells: expression of peptides and chromogranins.
       Histochemistry and cell biology. 2005 Jul;124(1):25-33
     • Wang H, Oxford G
       Voltage-dependent ion channels in CAD cells: A catecholaminergic neuronal line that exhibits inducible differentiation.
       Journal of neurophysiology. 2000 Dec;84(6):2888-95
     • Vortherms T, Watts V
       Sensitization of neuronal A2A adenosine receptors after persistent D2 dopamine receptor activation.
       The Journal of pharmacology and experimental therapeutics. 2004 Jan;308(1):221-7
     • Qi Y, Wang J, McMillian M, Chikaraishi D
       Characterization of a CNS cell line, CAD, in which morphological differentiation is initiated by serum deprivation.
       The Journal of neuroscience : the official journal of the Society for Neuroscience. 1997 Feb 15;17(4):1217-25
     • Wachira S, Hughes-Darden C, Taylor C, Ochillo R, Robinson T
       Evidence for the interaction of protein kinase C and melanocortin 3-receptor signaling pathways.
       Neuropeptides. 2003 Aug;37(4):201-10
     • Bilodeau M, Ji M, Paris M, Andrisani O
       Adenosine signaling promotes neuronal, catecholaminergic differentiation of primary neural crest cells and CNS-derived CAD cells.
       Molecular and cellular neurosciences. 2005 Jul;29(3):394-404
     • Li Y, Hou L, Aktiv A, Dahlström A
       Studies of the central nervous system-derived CAD cell line, a suitable model for intraneuronal transport studies?
       Journal of neuroscience research. 2007 Sep;85(12):2601-9
     • Lazaroff M, Qi Y, Chikaraishi D
       Differentiation of a catecholaminergic CNS cell line modifies tyrosine hydroxylase transcriptional regulation.
       Journal of neurochemistry. 1998 Jul;71(1):51-9
     • Dandoy-Dron F, Griffond B, Mishal Z, Tovey M, Dron M
       Scrg1, a novel protein of the CNS is targeted to the large dense-core vesicles in neuronal cells.
       The European journal of neuroscience. 2003 Nov;18(9):2449-59
     • Bae S, Xu Q, Hutchinson D, Colton C
       Y+ and y+ L arginine transporters in neuronal cells expressing tyrosine hydroxylase.
       Biochimica et biophysica acta. 2005 Aug 15;1745(1):65-73
     • Horton C, Qi Y, Chikaraishi D, Wang J
       Neurotrophin-3 mediates the autocrine survival of the catecholaminergic CAD CNS neuronal cell line.
       Journal of neurochemistry. 2001 Jan;76(1):201-9
     • Mima K, Deguchi S, Yamauchi T
       Characterization of 5' flanking region of alpha isoform of rat Ca2+/calmodulin-dependent protein kinase II gene and neuronal cell type specific promoter activity.
       Neuroscience letters. 2001 Jul 13;307(2):117-21
     • Hashemi S, Li J, Faigle R, Dahlström A
       Adrenergic differentiation and SSR2a receptor expression in CAD-cells cultured in serum-free medium.
       Neurochemistry international. 2003 Jan;42(1):9-17
     • Chen S, Ji M, Paris M, Hullinger R, Andrisani O
       The cAMP pathway regulates both transcription and activity of the paired homeobox transcription factor Phox2a required for development of neural crest-derived and central nervous system-derived catecholaminergic neurons.
       The Journal of biological chemistry. 2005 Dec 9;280(49):41025-36
     • Pasuit J, Li Z, Kuzhikandathil E
       Multi-modal regulation of endogenous D1 dopamine receptor expression and function in the CAD catecholaminergic cell line.
       Journal of neurochemistry. 2004 Jun;89(6):1508-19

     Genes/Proteins
     

     • Protein: Glial fibrillary acidic protein [Mus musculus]
  2. CAD cells are a useful model system for studying intracellular transport, including axonal transport.

     SHOW Details   Supporting(12)     Genes/Proteins: (8)

     Description: Studies using CAD cells have characterized novel myosin motors (e.g., myosin-X) and identified kinesin-1 cargos (e.g., the JNK-interacting proteins, JIP-1, JIP-2, and JIP-3, alcadein, and torsinA) and activators (e.g., the fasciculation and elongation protein zeta 1 (FEZ1)). CAD cells have also been used for studying axonal transport of signaling complexes (e.g., the JIP-1/JIP-3/JNK complex) and disease-relevant cargoes (e.g., APP). CAD cells have been shown to possess neuron-specific, cytoskeleton-associated proteins, and synaptic vesicle proteins.
     Experimental Approach: Mechanism - biochemistry and structural biology,   Animal models,   Mechanism - molecular and cell,  
     Pathogenic Narrative Tags: Perturbation
     Supporting Evidence
     

     • Berg J, Cheney R
       Myosin-X is an unconventional myosin that undergoes intrafilopodial motility.
       Nature cell biology. 2002 Mar;4(3):246-50
     • Li Y, Hou L, Aktiv A, Dahlström A
       Studies of the central nervous system-derived CAD cell line, a suitable model for intraneuronal transport studies?
       Journal of neuroscience research. 2007 Sep;85(12):2601-9
     • Kamm C, Boston H, Hewett J, Wilbur J, Corey D, Hanson P, Ramesh V, Breakefield X
       The early onset dystonia protein torsinA interacts with kinesin light chain 1.
       The Journal of biological chemistry. 2004 May 7;279(19):19882-92
     • Hammond J, Griffin K, Jih G, Stuckey J, Verhey K
       Co-operative versus independent transport of different cargoes by Kinesin-1.
       Traffic (Copenhagen, Denmark). 2008 May;9(5):725-41
     • Blasius T, Cai D, Jih G, Toret C, Verhey K
       Two binding partners cooperate to activate the molecular motor Kinesin-1.
       The Journal of cell biology. 2007 Jan 1;176(1):11-7
     • Sousa A, Berg J, Robertson B, Meeker R, Cheney R
       Myo10 in brain: developmental regulation, identification of a headless isoform and dynamics in neurons.
       Journal of cell science. 2006 Jan 1;119(Pt 1):184-94
     • Muresan Z, Muresan V
       c-Jun NH2-terminal kinase-interacting protein-3 facilitates phosphorylation and controls localization of amyloid-beta precursor protein.
       The Journal of neuroscience : the official journal of the Society for Neuroscience. 2005 Apr 13;25(15):3741-51
     • Verhey K, Meyer D, Deehan R, Blenis J, Schnapp B, Rapoport T, Margolis B
       Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules.
       The Journal of cell biology. 2001 Mar 5;152(5):959-70
     • Araki Y, Kawano T, Taru H, Saito Y, Wada S, Miyamoto K, Kobayashi H, Ishikawa H, Ohsugi Y, Yamamoto T, Matsuno K, Kinjo M, Suzuki T
       The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport.
       The EMBO journal. 2007 Mar 21;26(6):1475-86
     • Muresan Z, Muresan V
       A phosphorylated, carboxy-terminal fragment of beta-amyloid precursor protein localizes to the splicing factor compartment.
       Human molecular genetics. 2004 Mar 1;13(5):475-88
     • Muresan V, Varvel N, Lamb B, Muresan Z
       The cleavage products of amyloid-beta precursor protein are sorted to distinct carrier vesicles that are independently transported within neurites.
       The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009 Mar 18;29(11):3565-78
     • Muresan Z, Muresan V
       Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1.
       The Journal of cell biology. 2005 Nov 21;171(4):615-25

     Genes/Proteins
     

     • Protein: C-jun-amino-terminal kinase-interacting protein 2 [Mus musculus]
     • Protein: Torsin-1A [Mus musculus]
     • Protein: Mitogen-activated protein kinase 10 [Mus musculus]
     • Protein: C-jun-amino-terminal kinase-interacting protein 1 [Mus musculus]
     • Protein: C-jun-amino-terminal kinase-interacting protein 3 [Mus musculus]
     • Protein: Fasciculation and elongation protein zeta-1 [Mus musculus]
     • Protein: Calsyntenin-1 [Mus musculus]
     • Protein: Kinesin-1 heavy chain [Mus musculus]
  3. CAD cells are a useful model system for studying the switching from microtubule- to actin-based transport.

     SHOW Details   Supporting(2) 

     Description: Some cargos reach their destination by being successively transported on microtubules and actin filaments. A typical situation occurs in neuronal growth cones, where stable microtubules penetrate poorly into the distal lamellipodium and filopodia. These are actin-rich regions where transport is powered by myosin motors rather than kinesins. The mechanisms of switching between microtubule- and actin-based transport are poorly understood, and their study has been hampered by the lack of identified cargo proteins that use both microtubules and actin filaments to reach their final destination. We have recently identified the phosphorylated CTFs (pCTFs) as potential candidates for such a cargo in CAD cells. The pCTFs are transported to the growth cone by the microtubule motor kinesin-1, and then switch to transport along actin filaments, likely powered by myosin-X, within the lamellipodium and filopodia.
     Experimental Approach: Mechanism - biochemistry and structural biology,   Animal models,   Mechanism - molecular and cell
     Pathogenic Narrative Tags: Perturbation
     Supporting Evidence
     

     • Muresan V, Varvel N, Lamb B, Muresan Z
       The cleavage products of amyloid-beta precursor protein are sorted to distinct carrier vesicles that are independently transported within neurites.
       The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009 Mar 18;29(11):3565-78
     • Berg J, Cheney R
       Myosin-X is an unconventional myosin that undergoes intrafilopodial motility.
       Nature cell biology. 2002 Mar;4(3):246-50
  4. CAD cells are a useful model system for studying interneuronal transport through tunneling nanotubes.

     SHOW Details   Supporting(3) 

     Description: A recently identified, but still poorly characterized means of cell-to-cell communication is carried out via tunneling nanotubes that connect the cells. In addition to transferring signals, such intercellular bridges have been shown to enable cell-to-cell spreading of viral pathogens. Surprisingly, CAD cells form extensive tunneling nanotubes, which are used to transport vesicles of lysosomal origin and prions (when infected).
     Experimental Approach: Animal models,   Mechanism - biochemistry and structural biology,   Mechanism - molecular and cell
     Pathogenic Narrative Tags: Perturbation
     Supporting Evidence
     

     • Davis D, Sowinski S
       Membrane nanotubes: dynamic long-distance connections between animal cells.
       Nature reviews. Molecular cell biology. 2008 Jun;9(6):431-6
     • Sherer N, Lehmann M, Jimenez-Soto L, Horensavitz C, Pypaert M, Mothes W
       Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission.
       Nature cell biology. 2007 Mar;9(3):310-5
     • Gousset K, Schiff E, Langevin C, Marijanovic Z, Caputo A, Browman D, Chenouard N, de Chaumont F, Martino A, Enninga J, Olivo-Marin J, Männel D, Zurzolo C
       Prions hijack tunnelling nanotubes for intercellular spread.
       Nature cell biology. 2009 Mar;11(3):328-36
  5. CAD cells are a useful model system for studying neuronal signaling pathways.

     SHOW Details   Supporting(15) 

     Description: Studies using CAD cells have characterized signaling pathways that regulate differentiation and function of catecholaminergic neurons, and have identified novel intracellular signaling pathways that target disease-relevant proteins, such as APP.
     Experimental Approach: Animal models,   Mechanism - molecular and cell
     Pathogenic Narrative Tags: Perturbation
     Supporting Evidence
     

     • Wachira S, Hughes-Darden C, Taylor C, Ochillo R, Robinson T
       Evidence for the interaction of protein kinase C and melanocortin 3-receptor signaling pathways.
       Neuropeptides. 2003 Aug;37(4):201-10
     • Pasuit J, Li Z, Kuzhikandathil E
       Multi-modal regulation of endogenous D1 dopamine receptor expression and function in the CAD catecholaminergic cell line.
       Journal of neurochemistry. 2004 Jun;89(6):1508-19
     • Donai H, Nakamura M, Sogawa Y, Wang J, Urushihara M, Yamauchi T
       Involvement of Ca2+/calmodulin-dependent protein kinase II in neurite outgrowth induced by cAMP treatment and serum deprivation in a central nervous system cell line, CAD derived from rat brain.
       Neuroscience letters. 2000 Oct 27;293(2):111-4
     • Do T, Sun Q, Beuve A, Kuzhikandathil E
       Extracellular cAMP inhibits D1 dopamine receptor expression in CAD catecholaminergic cells via A2a adenosine receptors.
       Journal of neurochemistry. 2007 May;101(3):619-31
     • Vortherms T, Watts V
       Sensitization of neuronal A2A adenosine receptors after persistent D2 dopamine receptor activation.
       The Journal of pharmacology and experimental therapeutics. 2004 Jan;308(1):221-7
     • Benjanirut C, Paris M, Wang W, Hong S, Kim K, Hullinger R, Andrisani O
       The cAMP pathway in combination with BMP2 regulates Phox2a transcription via cAMP response element binding sites.
       The Journal of biological chemistry. 2006 Feb 3;281(5):2969-81
     • Xu Q, Wink D, Colton C
       Nitric oxide production and regulation of neuronal NOS in tyrosine hydroxylase containing neurons.
       Experimental neurology. 2004 Aug;188(2):341-50
     • Do T, Kerr B, Kuzhikandathil E
       Brain-derived neurotrophic factor regulates the expression of D1 dopamine receptors.
       Journal of neurochemistry. 2007 Jan;100(2):416-28
     • Bilodeau M, Ji M, Paris M, Andrisani O
       Adenosine signaling promotes neuronal, catecholaminergic differentiation of primary neural crest cells and CNS-derived CAD cells.
       Molecular and cellular neurosciences. 2005 Jul;29(3):394-404
     • Hashemi S, Li J, Faigle R, Dahlström A
       Adrenergic differentiation and SSR2a receptor expression in CAD-cells cultured in serum-free medium.
       Neurochemistry international. 2003 Jan;42(1):9-17
     • Dipace C, Sung U, Binda F, Blakely R, Galli A
       Amphetamine induces a calcium/calmodulin-dependent protein kinase II-dependent reduction in norepinephrine transporter surface expression linked to changes in syntaxin 1A/transporter complexes.
       Molecular pharmacology. 2007 Jan;71(1):230-9
     • Muresan Z, Muresan V
       c-Jun NH2-terminal kinase-interacting protein-3 facilitates phosphorylation and controls localization of amyloid-beta precursor protein.
       The Journal of neuroscience : the official journal of the Society for Neuroscience. 2005 Apr 13;25(15):3741-51
     • Muresan Z, Muresan V
       The amyloid-beta precursor protein is phosphorylated via distinct pathways during differentiation, mitosis, stress, and degeneration.
       Molecular biology of the cell. 2007 Oct;18(10):3835-44
     • Arboleda G, Huang T, Waters C, Verkhratsky A, Fernyhough P, Gibson R
       Insulin-like growth factor-1-dependent maintenance of neuronal metabolism through the phosphatidylinositol 3-kinase-Akt pathway is inhibited by C2-ceramide in CAD cells.
       The European journal of neuroscience. 2007 May;25(10):3030-8
     • Chen S, Ji M, Paris M, Hullinger R, Andrisani O
       The cAMP pathway regulates both transcription and activity of the paired homeobox transcription factor Phox2a required for development of neural crest-derived and central nervous system-derived catecholaminergic neurons.
       The Journal of biological chemistry. 2005 Dec 9;280(49):41025-36
  6. CAD cells are a useful model system for studying neurite retraction and retrodifferentiation.

     SHOW Details   Supporting(1) 

     Description: CAD cells can be maintained in differentiated state in culture in serum-free medium over extended periods of time. Upon addition of serum, CAD cells gradually retract their processes until they disappear, and re-enter the cell cycle.
     Experimental Approach: Mechanism - molecular and cell,   Animal models
     Pathogenic Narrative Tags: Perturbation
     Supporting Evidence
     

     • Qi Y, Wang J, McMillian M, Chikaraishi D
       Characterization of a CNS cell line, CAD, in which morphological differentiation is initiated by serum deprivation.
       The Journal of neuroscience : the official journal of the Society for Neuroscience. 1997 Feb 15;17(4):1217-25
  7. CAD cells are a useful model system for studying cellular processes related Alzheimer’s disease pathology, including post-translational processing of APP and intraneuronal oligomerization of Aβ.

     SHOW Details   Supporting(8) 

     Description: CAD cells have been used to study the proteolytic processing by secretases, and the phosphorylation of APP, in conditions relevant to Alzheimer’s disease. CAD cells are prone to intracellular oligomerization and neuritic accumulation of Aβ, and have been used to study these processes in relation to Alzheimer’s disease. CAD cells also secrete Aβ and soluble, N-terminal fragments (sAPPs) into the medium. Since the issue of the neuronal toxicity of secreted versus intracellular, oligomeric Aβ is one of the hottest topics in AD research, CAD cells may offer a novel system to test these two hypotheses.
     Experimental Approach: Mechanism - biochemistry and structural biology,   Pathophysiology,   Mechanism - molecular and cell
     Pathogenic Narrative Tags: Pathogenic event
     Supporting Evidence
     

     • Muresan Z, Muresan V
       Neuritic deposits of amyloid-beta peptide in a subpopulation of central nervous system-derived neuronal cells.
       Molecular and cellular biology. 2006 Jul;26(13):4982-97
     • Lee M, Kao S, Lemere C, Xia W, Tseng H, Zhou Y, Neve R, Ahlijanian M, Tsai L
       APP processing is regulated by cytoplasmic phosphorylation.
       The Journal of cell biology. 2003 Oct 13;163(1):83-95
     • Muresan Z, Muresan V
       Seeding neuritic plaques from the distance: a possible role for brainstem neurons in the development of Alzheimer's disease pathology.
       Neuro-degenerative diseases. 2008;5(3-4):250-3
     • Muresan Z, Muresan V
       A phosphorylated, carboxy-terminal fragment of beta-amyloid precursor protein localizes to the splicing factor compartment.
       Human molecular genetics. 2004 Mar 1;13(5):475-88
     • LaFerla F, Green K, Oddo S
       Intracellular amyloid-beta in Alzheimer's disease.
       Nature reviews. Neuroscience. 2007 Jul;8(7):499-509
     • Muresan Z, Muresan V
       c-Jun NH2-terminal kinase-interacting protein-3 facilitates phosphorylation and controls localization of amyloid-beta precursor protein.
       The Journal of neuroscience : the official journal of the Society for Neuroscience. 2005 Apr 13;25(15):3741-51
     • Haass C, Selkoe D
       Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.
       Nature reviews. Molecular cell biology. 2007 Feb;8(2):101-12
     • Muresan Z, Muresan V
       The amyloid-beta precursor protein is phosphorylated via distinct pathways during differentiation, mitosis, stress, and degeneration.
       Molecular biology of the cell. 2007 Oct;18(10):3835-44
  8. CAD cell are a useful model for studying a potential role of brainstem neurons in the initiation of neuritic plaques in Alzheimer’s disease.

     SHOW Details   Supporting(2)   Consistent(2) 

     Experimental Approach: Animal models,   Pathophysiology,  
     Pathogenic Narrative Tags: Perturbation
     Supporting Evidence
     

     • Muresan Z, Muresan V
       Neuritic deposits of amyloid-beta peptide in a subpopulation of central nervous system-derived neuronal cells.
       Molecular and cellular biology. 2006 Jul;26(13):4982-97
     • Muresan Z, Muresan V
       Seeding neuritic plaques from the distance: a possible role for brainstem neurons in the development of Alzheimer's disease pathology.
       Neuro-degenerative diseases. 2008;5(3-4):250-3

     Consistent statements
     

     • Brainstem neurons are initiators of neuritic plaques. Muresan Z  Muresan V 
     • Cultured neuronal cells originating from the brainstem - but not neurons derived from the cerebral cortex or hippocampus - accumulate oligomerized Aβ at the terminals of their processes. Muresan Z  Muresan V 
  9. CAD cells are a useful model system for studying a variety of neurodegenerative diseases and neurological disorders.

     SHOW Details   Supporting(8)     Genes/Proteins: (2)

     Description: CAD cells have been used to study the intracellular accumulation of mutant torsinA (the protein responsible for early-onset torsion dystonia) and Scrg1, a CNS protein relevant to Creutzfeldt-Jacob disease. Moreover, CAD cells have been shown to efficiently replicate prion strains, upon infection. CAD cells have also been used to investigate neurodegeneration at high APP expression levels, a condition relevant to Down’s syndrome. In addition, CAD cells have been used to study apoptosis, as a likely mechanism of cell death in many neurodegenerative diseases. Finally, CAD cells may be used to study the deregulation of dopamine signaling that is typical for several neurological disorders (e.g., Parkinson’s disease, Huntington’s disease, schizophrenia, attention deficit hyperactivity disorder, drug addiction).
     Experimental Approach: Mechanism - molecular and cell,   Pathophysiology,   Mechanism - biochemistry and structural biology
     Pathogenic Narrative Tags: Pathogenic event
     Supporting Evidence
     

     • Hewett J, Gonzalez-Agosti C, Slater D, Ziefer P, Li S, Bergeron D, Jacoby D, Ozelius L, Ramesh V, Breakefield X
       Mutant torsinA, responsible for early-onset torsion dystonia, forms membrane inclusions in cultured neural cells.
       Human molecular genetics. 2000 May 22;9(9):1403-13
     • Gousset K, Schiff E, Langevin C, Marijanovic Z, Caputo A, Browman D, Chenouard N, de Chaumont F, Martino A, Enninga J, Olivo-Marin J, Männel D, Zurzolo C
       Prions hijack tunnelling nanotubes for intercellular spread.
       Nature cell biology. 2009 Mar;11(3):328-36
     • Dandoy-Dron F, Griffond B, Mishal Z, Tovey M, Dron M
       Scrg1, a novel protein of the CNS is targeted to the large dense-core vesicles in neuronal cells.
       The European journal of neuroscience. 2003 Nov;18(9):2449-59
     • Do T, Kerr B, Kuzhikandathil E
       Brain-derived neurotrophic factor regulates the expression of D1 dopamine receptors.
       Journal of neurochemistry. 2007 Jan;100(2):416-28
     • Mahal S, Baker C, Demczyk C, Smith E, Julius C, Weissmann C
       Prion strain discrimination in cell culture: the cell panel assay.
       Proceedings of the National Academy of Sciences of the United States of America. 2007 Dec 26;104(52):20908-13
     • Muresan Z, Muresan V
       The amyloid-beta precursor protein is phosphorylated via distinct pathways during differentiation, mitosis, stress, and degeneration.
       Molecular biology of the cell. 2007 Oct;18(10):3835-44
     • Arboleda G, Waters C, Gibson R
       Metabolic activity: a novel indicator of neuronal survival in the murine dopaminergic cell line CAD.
       Journal of molecular neuroscience : MN. 2005;27(1):65-77
     • Arboleda G, Waters C, Gibson R
       Inhibition of caspases but not of calpains temporarily protect against C2-ceramide-induced death of CAD cells.
       Neuroscience letters. 2007 Jun 29;421(3):245-9

     Genes/Proteins
     

     • Protein: Scrapie-responsive protein 1 [Mus musculus]
     • Protein: Torsin-1A [Mus musculus]
  10. Experimental manipulation of CAD cells is easier, compared to primary neurons.

      SHOW Details   Supporting(2) 

      Description: CAD cells can be maintained for weeks in a differentiated state in culture, when they develop an elaborate network of neurites, and maintain their neuronal phenotype. CAD cells are easily transfectable, with high transfection efficiencies (using Roche’s Fugene6 or Amaxa’s Nucleofector device), and amenable to the generation of stably transfected cell lines. The resolution achieved by fluorescence microscopy in the thin processes of CAD cells allows resolving individual transport packages even without the use of confocal microscopy, making them ideal for studying intraneuritic transport.
      Experimental Approach: Mechanism - biochemistry and structural biology,   Mechanism - molecular and cell
      Pathogenic Narrative Tags: Perturbation
      Supporting Evidence
      

      • Qi Y, Wang J, McMillian M, Chikaraishi D
        Characterization of a CNS cell line, CAD, in which morphological differentiation is initiated by serum deprivation.
        The Journal of neuroscience : the official journal of the Society for Neuroscience. 1997 Feb 15;17(4):1217-25
      • Muresan Z, Muresan V
        Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1.
        The Journal of cell biology. 2005 Nov 21;171(4):615-25
• Cites as supporting evidence:
  • Muresan Z, Muresan V
    Neuritic deposits of amyloid-beta peptide in a subpopulation of central nervous system-derived neuronal cells.
    Molecular and cellular biology. 2006 Jul;26(13):4982-97
  • Muresan Z, Muresan V
    Seeding neuritic plaques from the distance: a possible role for brainstem neurons in the development of Alzheimer's disease pathology.
    Neuro-degenerative diseases. 2008;5(3-4):250-3
  • Muresan Z, Muresan V
    A phosphorylated, carboxy-terminal fragment of beta-amyloid precursor protein localizes to the splicing factor compartment.
    Human molecular genetics. 2004 Mar 1;13(5):475-88
  • Muresan Z, Muresan V
    Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1.
    The Journal of cell biology. 2005 Nov 21;171(4):615-25
  • Muresan Z, Muresan V
    The amyloid-beta precursor protein is phosphorylated via distinct pathways during differentiation, mitosis, stress, and degeneration.
    Molecular biology of the cell. 2007 Oct;18(10):3835-44
  • Muresan Z, Muresan V
    c-Jun NH2-terminal kinase-interacting protein-3 facilitates phosphorylation and controls localization of amyloid-beta precursor protein.
    The Journal of neuroscience : the official journal of the Society for Neuroscience. 2005 Apr 13;25(15):3741-51
  • Muresan V, Varvel N, Lamb B, Muresan Z
    The cleavage products of amyloid-beta precursor protein are sorted to distinct carrier vesicles that are independently transported within neurites.
    The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009 Mar 18;29(11):3565-78
• Cites Life Science Entity:
  • Protein: C-jun-amino-terminal kinase-interacting protein 1 [Mus musculus]
  • Protein: C-jun-amino-terminal kinase-interacting protein 2 [Mus musculus]
  • Protein: C-jun-amino-terminal kinase-interacting protein 3 [Mus musculus]
  • Protein: Calsyntenin-1 [Mus musculus]
  • Protein: Fasciculation and elongation protein zeta-1 [Mus musculus]
  • Protein: Glial fibrillary acidic protein [Mus musculus]
  • Protein: Kinesin-1 heavy chain [Mus musculus]
  • Protein: Mitogen-activated protein kinase 10 [Mus musculus]
  • Protein: Scrapie-responsive protein 1 [Mus musculus]
  • Protein: Torsin-1A [Mus musculus]
• Curated by: Wong G 
• Created On: Thu, Jul 09 2009 22:44:27 EDT
• Last Modified On: Thu Jul 09 22:44:35 EDT 2009