Citron kinase, a RhoA effector, enhances HIV-1 virion production by modulating exocytosis.
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.
Loomis
Rebecca J
RJ
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, CB 7295, Chapel Hill, NC 27599, USA.
Holmes
Derek A
DA
Elms
Andrew
A
Solski
Patricia A
PA
Der
Channing J
CJ
Su
Lishan
L
D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis; D017353:Gene Deletion; D015683:Gene Products, gag / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016350:Leucine Zippers; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism*; D014779:Virus Replication; D016335:Zinc Fingers; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D015683:Gene Products, gag; D047908:Intracellular Signaling Peptides and Proteins; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases; D020742:rhoA GTP-Binding Protein