Arl5b is a Golgi-localised small G protein involved in the regulation of retrograde transport

Exp Cell Res. 2012 Mar 10;318(5):464-77. doi: 10.1016/j.yexcr.2011.12.023. Epub 2012 Jan 5.


Regulation of membrane transport is controlled by small G proteins, which include members of the Rab and Arf families. Whereas the role of the classic Arf family members are well characterized, many of the Arf-like proteins (Arls) remain poorly defined. Here we show that Arl5a and Arl5b are localised to the trans-Golgi in mammalian cells, and furthermore have identified a role for Arl5b in the regulation of retrograde membrane transport from endosomes to the trans-Golgi network (TGN). The constitutively active Arl5b (Q70L)-GFP mutant was localised efficiently to the Golgi in HeLa cells whereas the dominant-negative Arl5b (T30N)-GFP mutant was dispersed throughout the cytoplasm and resulted in perturbation of the Golgi apparatus. Stable HeLa cells expressing GFP-tagged Arl5b (Q70L) showed an increased rate of endosome-to-Golgi transport of the membrane cargo TGN38 compared with control HeLa cells. Depletion of Arl5b by RNAi resulted in an alteration in the intracellular distribution of mannose-6-phosphate receptor, and significantly reduced the endosome-to-TGN transport of the membrane cargo TGN38 and of Shiga toxin, but had no affect on the anterograde transport of the cargo E-cadherin. Collectively these results suggest that Arl5b is a TGN-localised small G protein that plays a key role in regulating transport along the endosome-TGN pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • ADP-Ribosylation Factors / physiology*
  • Amino Acid Substitution
  • Gene Knockdown Techniques
  • Golgi Apparatus / metabolism*
  • Golgi Matrix Proteins
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Mutant Proteins / metabolism
  • Protein Transport
  • RNA Interference
  • Receptor, IGF Type 2 / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Shiga Toxin / metabolism


  • GORASP1 protein, human
  • Golgi Matrix Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Mutant Proteins
  • Receptor, IGF Type 2
  • Recombinant Fusion Proteins
  • TGOLN2 protein, human
  • Green Fluorescent Proteins
  • Shiga Toxin
  • ARL5B protein, human
  • ADP-Ribosylation Factors
  • ARL5A protein, human