ARF1 and ARF4 regulate recycling endosomal morphology and retrograde transport from endosomes to the Golgi apparatus

Mol Biol Cell. 2013 Aug;24(16):2570-81. doi: 10.1091/mbc.E13-04-0197. Epub 2013 Jun 19.

Abstract

Small GTPases of the ADP-ribosylation factor (ARF) family, except for ARF6, mainly localize to the Golgi apparatus, where they trigger formation of coated carrier vesicles. We recently showed that class I ARFs (ARF1 and ARF3) localize to recycling endosomes, as well as to the Golgi, and are redundantly required for recycling of endocytosed transferrin. On the other hand, the roles of class II ARFs (ARF4 and ARF5) are not yet fully understood, and the complementary or overlapping functions of class I and class II ARFs have been poorly characterized. In this study, we find that simultaneous depletion of ARF1 and ARF4 induces extensive tubulation of recycling endosomes. Moreover, the depletion of ARF1 and ARF4 inhibits retrograde transport of TGN38 and mannose-6-phosphate receptor from early/recycling endosomes to the trans-Golgi network (TGN) but does not affect the endocytic/recycling pathway of transferrin receptor or inhibit retrograde transport of CD4-furin from late endosomes to the TGN. These observations indicate that the ARF1+ARF4 and ARF1+ARF3 pairs are both required for integrity of recycling endosomes but are involved in distinct transport pathways: the former pair regulates retrograde transport from endosomes to the TGN, whereas the latter is required for the transferrin recycling pathway from endosomes to the plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 1 / genetics
  • ADP-Ribosylation Factor 1 / metabolism*
  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • CD4 Antigens / metabolism
  • Cell Line, Tumor
  • Endosomes / metabolism*
  • Furin / metabolism
  • Golgi Apparatus / metabolism*
  • HeLa Cells
  • Humans
  • Membrane Glycoproteins / metabolism
  • Protein Transport
  • RNA Interference
  • RNA, Small Interfering
  • Receptor, IGF Type 2 / metabolism
  • Receptors, Transferrin / metabolism
  • rab GTP-Binding Proteins / metabolism
  • rab4 GTP-Binding Proteins / metabolism
  • trans-Golgi Network / metabolism

Substances

  • CD4 Antigens
  • Membrane Glycoproteins
  • RNA, Small Interfering
  • Receptor, IGF Type 2
  • Receptors, Transferrin
  • TGOLN2 protein, human
  • Furin
  • ARF3 protein, human
  • rab11 protein
  • ADP-Ribosylation Factor 1
  • ADP-Ribosylation Factors
  • ARF4 protein, human
  • ARF5 protein, human
  • rab GTP-Binding Proteins
  • rab4 GTP-Binding Proteins