Calsyntenins Mediate TGN Exit of APP in a Kinesin-1-Dependent Manner
| Autor: | Peter Streit, Kerstin Leuthäuser, Tu-My Diep, Jessica Blume, Peter Sonderegger, Alexander Ludwig, Ju Yuan, Martin Steuble, José María Mateos |
|---|---|
| Přispěvatelé: | University of Zurich, Sonderegger, P |
| Rok vydání: | 2009 |
| Předmět: |
1303 Biochemistry
Golgi Apparatus Kinesins macromolecular substances Biology Endoplasmic Reticulum Biochemistry 1307 Cell Biology Amyloid beta-Protein Precursor 03 medical and health sciences symbols.namesake 1315 Structural Biology 0302 clinical medicine 1311 Genetics Structural Biology Organelle 10019 Department of Biochemistry 1312 Molecular Biology Genetics Amyloid precursor protein Animals Humans Calsyntenin education Molecular Biology 030304 developmental biology 0303 health sciences education.field_of_study Endoplasmic reticulum Biological Transport Cell Biology Golgi apparatus Cell biology Kinesin light chain 1 symbols biology.protein 570 Life sciences biology Kinesin 030217 neurology & neurosurgery Intracellular trans-Golgi Network |
| Zdroj: | Traffic |
| ISSN: | 1600-0854 1398-9219 |
| Popis: | Kinesin motors are required for the export of membranous cargo from the trans-Golgi network (TGN), yet information about how kinesins are recruited to forming transport intermediates is sparse. Here we show that the Kinesin-1 docking protein calsyntenin-1 localizes to the TGN in vivo and directly and specifically recruits Kinesin-1 to Golgi/TGN membranes as well as to dynamic post-Golgi carriers. Overexpression of various calsyntenin chimeras and kinesin light chain 1 (KLC1) at high levels caused the formation of aberrant membrane stacks at the endoplasmic reticulum (ER) or the Golgi, disrupted overall Golgi structure and blocked exit of calsyntenin from the TGN. Intriguingly, this blockade of calsyntenin exit strongly and selectively impeded TGN exit of amyloid precursor protein (APP). Using live cell microscopy we found that calsyntenins exit the TGN in Kinesin-1-decorated tubular structures which may serve as carriers for calsyntenin-1-mediated post-TGN transport of APP. Abrogation of this pathway via virus-mediated knockdown of calsyntenin-1 expression in primary cultured neurons caused a marked elevation of APP C-terminal fragments. Together, these results indicate a role for calsyntenin-1 in Kinesin-1-dependent TGN exit and post-Golgi transport of APP-containing organelles and further suggest that distinct intracellular routes may exhibit different capacities for proteolytic processing of APP. |
| Databáze: | OpenAIRE |
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