Grp1-associated scaffold protein (GRASP) is a regulator of the ADP ribosylation factor 6 (Arf6)-dependent membrane trafficking pathway

Cell Biol Int. 2012;36(12):1115-28. doi: 10.1042/CBI20120221.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ADP-Ribosylation Factor 6
  • ADP-Ribosylation Factors / analysis
  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Endosomes / metabolism
  • Gene Expression
  • HeLa Cells
  • Humans
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Point Mutation
  • Protein Transport
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction
  • Up-Regulation
  • rab GTP-Binding Proteins / analysis
  • rab GTP-Binding Proteins / metabolism


  • ADP-Ribosylation Factor 6
  • Carrier Proteins
  • Membrane Proteins
  • Receptors, Cytoplasmic and Nuclear
  • phosphatidylinositol receptors
  • tamalin protein, human
  • rab11 protein
  • ADP-Ribosylation Factors
  • ARF6 protein, human
  • rab GTP-Binding Proteins