Header

UZH-Logo

Maintenance Infos

Calsyntenins mediate TGN exit of APP in a Kinesin-1-dependent manner


Ludwig, A; Blume, J; Diep, T M; Yuan, J; Mateos, J M; Leuthäuser, K; Steuble, M; Streit, P; Sonderegger, P (2009). Calsyntenins mediate TGN exit of APP in a Kinesin-1-dependent manner. Traffic, 10(5):572-589.

Abstract

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 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 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.

Abstract

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 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 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.

Statistics

Citations

Dimensions.ai Metrics
38 citations in Web of Science®
39 citations in Scopus®
60 citations in Microsoft Academic
Google Scholar™

Altmetrics

Downloads

33 downloads since deposited on 16 Apr 2009
10 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Structural Biology
Life Sciences > Biochemistry
Life Sciences > Molecular Biology
Life Sciences > Genetics
Life Sciences > Cell Biology
Language:English
Date:May 2009
Deposited On:16 Apr 2009 14:27
Last Modified:29 Jul 2020 18:53
Publisher:Wiley-Blackwell
ISSN:1398-9219
Additional Information:The definitive version is available at www.blackwell-synergy.com
OA Status:Green
Publisher DOI:https://doi.org/10.1111/j.1600-0854.2009.00886.x
PubMed ID:19192245

Download

Green Open Access

Download PDF  'Calsyntenins mediate TGN exit of APP in a Kinesin-1-dependent manner'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 37MB
View at publisher