Journal
PROTEOMICS
Volume 10, Issue 21, Pages 3775-3788Publisher
WILEY-BLACKWELL
DOI: 10.1002/pmic.201000384
Keywords
beta-Amyloid precursor protein; Axonal transport; Calsyntenin; alcadein; Cell biology; Endosomes; Kinesin-1
Funding
- Functional Genomics Center Zurich (FGCZ)
- Swiss National Science Foundation
- NCCR (National Center of Competence in Research) Neural Plasticity and Repair of the Swiss National Science Foundation
- Olga Mayenfisch Stiftung
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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 beta-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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