Molecular characterization of a trafficking organelle
Dissecting the axonal paths of calsyntenin-1 transport vesicles
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Date
2010
Publication Type
Journal Article
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yes
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Abstract
Kinesin motors play crucial roles in the delivery of membranous cargo to its destination and thus for the establishment and maintenance of cellular polarization. Recently, calsyntenin‐1 was identified as a cargo‐docking protein for Kinesin‐1‐mediated axonal transport of tubulovesicular organelles along axons of central nervous system neurons. To further define the function of calsyntenin‐1, we immunoisolated calsyntenin‐1 organelles from murine brain homogenates and determined their proteome by MS. We found that calsyntenin‐1 organelles are endowed with components of the endosomal trafficking machinery and contained the β‐amyloid precursor protein (APP). Detailed biochemical analyses of calsyntenin‐1 immunoisolates in conjunction with immunocytochemical colocalization studies with cultured hippocampal neurons, using endosomal marker proteins for distinct subcompartments of the endosomal pathways, indicated that neuronal axons contain at least two distinct, nonoverlapping calsyntenin‐1‐containing transport packages: one characterized as early‐endosomal, APP positive, the other as recycling‐endosomal, APP negative. We postulate that calsyntenin‐1 acts as a general mediator of anterograde axonal transportation of endosomal vesicles. In this role, calsyntenin‐1 may actively contribute to axonal growth and pathfinding in the developing as well as to the maintenance of neuronal polarity in the adult nervous system; further, it may actively contribute to the stabilization of APP during its anterograde axonal trajectory.
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published
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Journal / series
Proteomics
Volume
10 (21)
Pages / Article No.
3775 - 3788
Publisher
Wiley
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Subject
beta-Amyloid precursor protein; Axonal transport; Calsyntenin/alcadein; Cell biology; Endosomes; Kinesin-1
Organisational unit
02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
Notes
Received June 30 2010, Accepted August 3 2010, Published October 5 2010.