101. Molecular characterization of a trafficking organelle: dissecting the axonal paths of calsyntenin-1 transport vesicles
- Author
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Alexander Stephan, Beat Kunz, Peter Sonderegger, Tu-My Diep, Alexander Ludwig, Bertran Gerrits, Martin Steuble, José María Mateos, Peter Streit, Mitsuo Tagaya, Philipp Schätzle, University of Zurich, and Sonderegger, P
- Subjects
Proteomics ,Nervous system ,1303 Biochemistry ,Endosome ,Kinesins ,610 Medicine & health ,10071 Functional Genomics Center Zurich ,Endosomes ,Biology ,Hippocampus ,Biochemistry ,Amyloid beta-Protein Precursor ,Mice ,03 medical and health sciences ,Prosencephalon ,0302 clinical medicine ,Organelle ,10019 Department of Biochemistry ,1312 Molecular Biology ,medicine ,Amyloid precursor protein ,Animals ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Vesicle ,Calcium-Binding Proteins ,Colocalization ,Biological Transport ,Immunohistochemistry ,Axons ,Endocytosis ,Cell biology ,medicine.anatomical_structure ,nervous system ,biology.protein ,Axoplasmic transport ,570 Life sciences ,biology ,Kinesin ,Electrophoresis, Polyacrylamide Gel ,030217 neurology & neurosurgery - 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.
- Published
- 2010
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