Citron kinase, a RhoA effector, enhances HIV-1 virion production by modulating exocytosis

Traffic. 2006 Dec;7(12):1643-53. doi: 10.1111/j.1600-0854.2006.00503.x.

Abstract

RhoGTPases play important roles in the regulation of protein transport and membrane recycling. Little is known, however, about how RhoGTPases affect HIV-1 virion production, which is dependent on the endosomal sorting pathway. We report that ectopic expression of citron kinase (citron-K), a RhoA effector, preferentially enhances HIV-1 virion production. Depletion of endogenous citron-K inhibits HIV-1 virion production. Citron-N, which lacks the kinase domain, also enhances HIV-1 virion production. The leucine zipper, Rho-binding and zinc finger domains of citron-N are necessary for the enhancement activity. Citron-K also enhances murine leukemia virion production and the HIV-1 late domain is not required for the citron-K-mediated enhancement. Ectopic expression of citron-K leads to the formation of cytoplasmic structures containing citron-K and HIV-1 Gag proteins. HIV-1 and citron-K cooperatively enhance acidic endosome and lysosome compartments. Finally, citron-K promotes exocytosis of microvesicles or exosomes that co-purify with HIV-1 virions. We conclude that citron-K enhances HIV-1 virion production by stimulating the endosomal compartments and exocytosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Endosomes / metabolism
  • Exocytosis*
  • Gene Deletion
  • Gene Products, gag / deficiency
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leucine Zippers
  • Lysosomes / metabolism
  • Mice
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Virion / metabolism*
  • Virus Replication
  • Zinc Fingers
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Gene Products, gag
  • Intracellular Signaling Peptides and Proteins
  • citron-kinase
  • Protein Serine-Threonine Kinases
  • rhoA GTP-Binding Protein