Related Experiment Video
Updated: Jul 19, 2026
10:27
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
Integrins regulate Rac targeting by internalization of membrane domains
Miguel A del Pozo1, Nazilla B Alderson, William B Kiosses
1Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. mdelpozo@scripps.edu
Science (New York, N.Y.)
|February 7, 2004
Summary
Cell adhesion regulates Rac1 protein activity by controlling cholesterol-rich membrane domains. Integrin signals and lipid raft regulation are key to Rac1
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Rac1 translocation to the plasma membrane is crucial for activating downstream effectors.
- Integrin-mediated cell adhesion to the extracellular matrix is required for Rac1 activation.
Purpose of the Study:
- To investigate the role of membrane lipids and lipid rafts in Rac1 translocation.
- To understand how cell adhesion regulates Rac1 activity through membrane domain dynamics.
Main Methods:
- Studied the binding preference of active Rac1 to different membrane compositions.
- Investigated the effect of cell detachment on plasma membrane cholesterol and lipid raft markers.
- Examined the impact of preventing lipid raft internalization on Rac1 membrane targeting and effector activation.
Main Results:
- Active Rac1 preferentially binds to low-density, cholesterol-rich membranes.
- Cell detachment induces internalization of plasma membrane cholesterol and lipid raft markers.
- Inhibition of lipid raft internalization sustains Rac1 membrane targeting and effector activation in nonadherent cells.
Conclusions:
- Membrane lipid composition, particularly cholesterol content, influences Rac1 localization.
- Integrin signaling regulates lipid raft dynamics, controlling Rac1 activity in adherent cells.
- Targeting lipid raft regulation offers a potential strategy to modulate Rac1-dependent signaling pathways.
Related Concept Videos
02:22Regulated mRNA Transport
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...
01:45Regulation 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...
01:14Rab 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...
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...
01:34Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
01:26Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
01:21Cell Polarization by Rho Proteins
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...