Differential Regulation of Lipoprotein and Hepatitis C Virus Secretion by Rab1b

Cell Rep. 2017 Oct 10;21(2):431-441. doi: 10.1016/j.celrep.2017.09.053.


Secretory cells produce diverse cargoes, yet how they regulate concomitant secretory traffic remains insufficiently explored. Rab GTPases control intracellular vesicular transport. To map secretion pathways, we generated a library of lentivirus-expressed dominant-negative Rab mutants and used it in a large-scale screen to identify regulators of hepatic lipoprotein secretion. We identified several candidate pathways, including those mediated by Rab11 and Rab8. Surprisingly, inhibition of Rab1b, the major regulator of transport from the endoplasmic reticulum to the Golgi, differently affected the secretion of the very-low-density lipoprotein components ApoE and ApoB100, despite their final association on mature secreted lipoprotein particles. Since hepatitis C virus (HCV) incorporates ApoE and ApoB100 into its virus particle, we also investigated infectious HCV secretion and show that its regulation by Rab1b mirrors that of ApoB100. These observations reveal differential regulation of hepatocyte secretion by Rab1b and advance our understanding of lipoprotein assembly and lipoprotein and HCV secretion.

Keywords: GTPase; HCV; Rab; albumin; apolipoprotein; hepatitis; hepatocyte; lipoprotein; secretion; transport.

MeSH terms

  • Apolipoproteins / metabolism*
  • Cell Line, Tumor
  • Exocytosis
  • HEK293 Cells
  • Hepacivirus / metabolism
  • Humans
  • Mutation
  • Secretory Pathway*
  • rab1 GTP-Binding Proteins / genetics
  • rab1 GTP-Binding Proteins / metabolism*


  • Apolipoproteins
  • Rab1B protein, human
  • rab1 GTP-Binding Proteins