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

作者：Houghton Fiona J; Bellingham Shayne A; Hill Andrew F; Bourges Dorothee; Ang Desmond K Y; Gemetzis Timothy; Gasnereau Isabelle; Gleeson Paul A^*

来源：Experimental Cell Research, 2012, 318(5): 464-477.

DOI：10.1016/j.yexcr.2011.12.023

• Art proteins
• trans-Golgi network
• Membrane transport
• Retrograde transport
• TGN38
• Shiga toxin

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 (Arts) 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.

• 出版日期2012-3-10