Related Experiment Video

Updated: Apr 13, 2026

Visualization of HIV-1 Gag Binding to Giant Unilamellar Vesicle GUV Membranes
08:21

Visualization of HIV-1 Gag Binding to Giant Unilamellar Vesicle GUV Membranes

Published on: July 28, 2016

9.6K

Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate

Pehuén Pereyra Gerber1, Mercedes Cabrini1, Carolina Jancic2

  • 1Instituto de Investigaciones Biomédicas en Retrovirus y Síndrome de Inmunodeficiencia Adquirida (INBIRS)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, C1121ABG Buenos Aires, Argentina.

The Journal of Cell Biology
|May 6, 2015
PubMed

Insights

Rab27a protein controls HIV-1 assembly by directing PI4KIIα-carrying endosomes to the cell membrane. This ensures sufficient PI(4,5)P2 for viral Gag polyprotein binding and subsequent HIV-1 replication.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • HIV-1 assembly requires the viral Gag polyprotein to associate with the plasma membrane (PM).
  • Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is crucial for Gag binding and HIV-1 replication.
  • The precise mechanisms regulating PI(4,5)P2 levels at the PM during HIV-1 assembly are not fully understood.

Purpose of the Study:

  • To investigate the role of Rab27a in regulating PI(4,5)P2 production at the plasma membrane.
  • To identify Rab27a effectors involved in HIV-1 assembly.
  • To elucidate the pathway controlling Gag polyprotein recruitment to the PM.

Main Methods:

  • Cellular trafficking assays in CD4(+) T cells and macrophages.
  • Analysis of protein-protein interactions and localization.
  • Screening of Rab27a effectors using genetic and biochemical approaches.

Main Results:

  • Rab27a directs late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) to the PM.
  • Rab27a promotes localized PI(4,5)P2 production, enhancing Pr55(Gag) membrane association.
  • Slp2a, Slp3, and Slac2b are identified as Rab27a effectors required for Gag-PM association, with Slp2a cooperating in PI4KIIα recruitment.

Conclusions:

  • Rab27a is a key regulator of PI(4,5)P2 homeostasis at the PM during HIV-1 replication.
  • The Rab27a-mediated trafficking of PI4KIIα-positive endosomes is essential for HIV-1 assembly.
  • Targeting this pathway could offer new strategies for controlling HIV-1 replication.

More Related Videos

PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions10:58

PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions

Published on: July 27, 2017

10.1K
Detection of Viral RNA by Fluorescence in situ Hybridization FISH10:16

Detection of Viral RNA by Fluorescence in situ Hybridization FISH

Published on: May 5, 2012

39.7K

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
10.7K
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
35
Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
4.8K
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
5.2K
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
5.5K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.5K