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Kinesin KIF4 Regulates Intracellular Trafficking and Stability of the Human Immunodeficiency Virus Type 1 Gag Polyprotein▿ †
- Publication Year :
- 2008
- Publisher :
- American Society for Microbiology (ASM), 2008.
-
Abstract
- Retroviral Gag proteins are synthesized as soluble, myristoylated precursors that traffic to the plasma membrane and promote viral particle production. The intracellular transport of human immunodeficiency virus type 1 (HIV-1) Gag to the plasma membrane remains poorly understood, and cellular motor proteins responsible for Gag movement are not known. Here we show that disrupting the function of KIF4, a kinesin family member, slowed temporal progression of Gag through its trafficking intermediates and inhibited virus-like particle production. Knockdown of KIF4 also led to increased Gag degradation, resulting in reduced intracellular Gag protein levels; this phenotype was rescued by reintroduction of KIF4. When KIF4 function was blocked, Gag transiently accumulated in discrete, perinuclear, nonendocytic clusters that colocalized with endogenous KIF4, with Ubc9, an E2 SUMO-1 conjugating enzyme, and with SUMO. These studies identify a novel transit station through which Gag traffics en route to particle assembly and highlight the importance of KIF4 in regulating HIV-1 Gag trafficking and stability.
- Subjects :
- Cytoplasm
viruses
Recombinant Fusion Proteins
Immunology
SUMO-1 Protein
Kinesins
Biology
Microbiology
gag Gene Products, Human Immunodeficiency Virus
Virus
Motor protein
Virology
Chlorocebus aethiops
Animals
Humans
RNA, Small Interfering
Myristoylation
Gene knockdown
Structure and Assembly
Group-specific antigen
Phenotype
Molecular biology
Cell biology
Protein Transport
Insect Science
COS Cells
Ubiquitin-Conjugating Enzymes
HIV-1
Kinesin
Intracellular
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....d7dccfca3f777ede0538eb497abd0c93