Department of Pharmacology, University of Pennsylvania School of Medicine, 835 BRB 421 Curie Blvd, Philadelphia, PA 19104, U.S.A.
Grp1-associated scaffold protein (GRASP) is a regulator of the ADP ribosylation factor 6 (Arf6)-dependent membrane trafficking pathway
Article first published online: 2 JAN 2013
© The Author(s) Journal compilation © 2012 International Federation for Cell Biology
Cell Biology International
Volume 36, Issue 12, pages 1115–1128, December 2012
How to Cite
Venkataraman, A., Nevrivy, D. J., Filtz, T. M. and Leid, M. (2012), Grp1-associated scaffold protein (GRASP) is a regulator of the ADP ribosylation factor 6 (Arf6)-dependent membrane trafficking pathway. Cell Biology International, 36: 1115–1128. doi: 10.1042/CBI20120221
- Issue published online: 2 JAN 2013
- Article first published online: 2 JAN 2013
- Received 11 May 2012/28 June 2012; Accepted 29 August 2012
- scaffold protein; trafficking
GRASP interacts with Grp1 (general receptor for phosphoinositides 1; cytohesin 3), which catalyses nucleotide exchange on and activation of Arf6 (ADP-ribosylation factor-6). Arf6 is a low-molecular-mass GTPase that regulates key aspects of endocytic recycling pathways. Overexpressed GRASP accumulated in the juxtanuclear ERC (endocytic recycling compartment). GRASP co-localized with a constitutively inactive mutant of Arf6 in the ERC such that it was reversed by expression of wild-type Grp1. Co-expression of GRASP and Grp1 promoted membrane ruffling, a cellular hallmark of Arf6 activation. GRASP accumulation in ERC was found to block recycling of the MHC-I (major histocompatibility complex-I), which is trafficked by the Arf6-dependent pathway. In contrast, overexpression of GRASP had no effect on the recycling of transferrin receptors, which are trafficked by a clathrin-dependent pathway. The findings suggest that GRASP regulates the non-clathrin/Arf6-dependent, plasma membrane recycling and signalling pathways.