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• The cleavage products of amyloid-beta precursor protein are sorted to distinct carrier vesicles that are independently transported within neurites.
• Citation:
  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
  [PubMed] [Alzforum]
• Supporting:
  • 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
  • CAD cells are a useful model for studies of APP cell biology and Alzheimers disease pathology, including Aβ accumulation within neurites.

    SHOW Details   Supporting(7) 

    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.
    Contained Discourse: 10 Elements
    Experimental Approach:
    Pathogenic Narrative Tags:
    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
      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
      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
      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
  • 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 1 [Mus musculus]
    • Protein: C-jun-amino-terminal kinase-interacting protein 2 [Mus musculus]
    • Protein: Kinesin-1 heavy chain [Mus musculus]
    • Protein: Torsin-1A [Mus musculus]
    • Protein: Calsyntenin-1 [Mus musculus]
    • Protein: Mitogen-activated protein kinase 10 [Mus musculus]
    • Protein: C-jun-amino-terminal kinase-interacting protein 3 [Mus musculus]
    • Protein: Fasciculation and elongation protein zeta-1 [Mus musculus]
• Created On: Tue, Jul 07 13:42:51 EDT 2009
• Last Modified On: Tue Jul 07 13:42:51 EDT 2009