Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-18250

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.

[img]
Preview
Accepted Version
PDF
36Mb

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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Biochemistry
07 Faculty of Science > Institute of Biochemistry
DDC:570 Life sciences; biology
Language:English
Date:May 2009
Deposited On:16 Apr 2009 16:27
Last Modified:28 Nov 2013 00:53
Publisher:Wiley-Blackwell
ISSN:1398-9219
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:10.1111/j.1600-0854.2009.00886.x
PubMed ID:19192245
Citations:Web of Science®. Times Cited: 18
Google Scholar™

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page