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Molecular characterization of a trafficking organelle: Dissecting the axonal paths of calsyntenin‐1 transport vesicles
Author(s) -
Steuble Martin,
Gerrits Bertran,
Ludwig Alexander,
Mateos José María,
Diep TuMy,
Tagaya Mitsuo,
Stephan Alexander,
Schätzle Philipp,
Kunz Beat,
Streit Peter,
Sonderegger Peter
Publication year - 2010
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201000384
Subject(s) - kinesin , endosome , axoplasmic transport , organelle , microbiology and biotechnology , biology , colocalization , growth cone , vesicle , molecular motor , transport protein , motor protein , microtubule , neuroscience , axon , biochemistry , intracellular , membrane
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.