title: Grp1-associated scaffold protein (GRASP) is a regulator of the ADP ribosylation factor 6 (Arf6)-dependent membrane trafficking pathway.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Venkataraman
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Nevrivy
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Filtz
authors.forename: Mark
authors.initials: M
authors.lastname: Leid
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D002352:Carrier Proteins; D008565:Membrane Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C040985:phosphatidylinositol receptors; C410230:tamalin protein, human; C000715348:ARF6 protein, human