ARL4A acts with GCC185 to modulate Golgi complex organization

J Cell Sci. 2011 Dec 1;124(Pt 23):4014-26. doi: 10.1242/jcs.086892. Epub 2011 Dec 8.


ADP-ribosylation factor-like protein 4A (ARL4A) is a developmentally regulated member of the ARF/ARL GTPase family. The primary structure of ARL4A is very similar to that of other ARF/ARL molecules, but its function remains unclear. The trans-Golgi network golgin GCC185 is required for maintenance of Golgi structure and distinct endosome-to-Golgi transport. We show here that GCC185 acts as a new effector for ARL4 to modulate Golgi organization. ARL4A directly interacts with GCC185 in a GTP-dependent manner. Sub-coiled-coil regions of the CC2 domain of GCC185 are required for the interaction between GCC185 and ARL4A. Depletion of ARL4A reproduces the GCC185-depleted phenotype, causing fragmentation of the Golgi compartment and defects in endosome-to-Golgi transport. GCC185 and ARL4A localize to the Golgi independently of each other. Deletion of the ARL4A-interacting region of GCC185 results in inability to maintain Golgi structure. Depletion of ARL4A impairs the interaction between GCC185 and cytoplasmic linker-associated proteins 1 and 2 (CLASP1 and CLASP2, hereafter CLASPs) in vivo, and abolishes the GCC185-mediated Golgi recruitment of these CLASPs, which is crucial for the maintenance of Golgi structure. In summary, we suggest that ARL4A alters the integrity of the Golgi structure by facilitating the interaction of GCC185 with CLASPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / metabolism*
  • Amino Acid Sequence
  • Endosomes / metabolism
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / physiology*
  • Golgi Matrix Proteins
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / metabolism
  • Protein Interaction Domains and Motifs
  • Protein Transport
  • Sequence Deletion
  • Substrate Specificity
  • Transfection
  • Two-Hybrid System Techniques


  • CLASP1 protein, human
  • CLASP2 protein, human
  • GCC2 protein, human
  • Golgi Matrix Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • ADP-Ribosylation Factors
  • ARL4A protein, human