Microtubule-dependent regulation of Rho GTPases during internalisation of Yersinia pseudotuberculosis

Karen McGee1, Per Holmfeldt, Maria Fällman

  • 1Department of Molecular Biology, Umeå University, 901 87, Umeå, Sweden.

FEBS Letters
|December 31, 2002
PubMed

Insights

Microtubules regulate Rho GTPases during Yersinia pseudotuberculosis uptake. Disrupting microtubules suppressed bacterial internalization, but Vav2 expression prevented this effect, highlighting its role in Rho GTPase activation.

Area of Science:

  • Cell Biology
  • Microbiology
  • Molecular Biology

Background:

  • Yersinia pseudotuberculosis internalizes into host cells through bacterial invasin binding to beta1 integrins.
  • This process relies on the actin cytoskeleton and various signaling molecules, including Src family kinases and Rho GTPases.

Purpose of the Study:

  • To investigate the role of the microtubule system in regulating Rho GTPases during Yersinia pseudotuberculosis uptake.
  • To elucidate the involvement of Vav2, a guanine nucleotide exchange factor, in this process.

Main Methods:

  • Utilizing HeLa cells and treating them with microtubule-disrupting agents (nocodazole, paclitaxel).
  • Manipulating Rho GTPase (Rac, Cdc42, RhoG, RhoA) and Vav2 expression levels.
  • Overexpressing p50 dynamitin to assess its impact on bacterial uptake.

Main Results:

  • Microtubule disruption significantly suppressed Yersinia pseudotuberculosis uptake.
  • Overexpression of specific Rho GTPases partially rescued the uptake defect caused by nocodazole.
  • Vav2 expression completely prevented the inhibitory effect of nocodazole and also blocked the effect of p50 dynamitin.

Conclusions:

  • Microtubules play a crucial role in regulating Rho GTPases during Yersinia pseudotuberculosis-mediated phagocytosis.
  • Vav2 acts as a key guanine nucleotide exchange factor that can functionally substitute for microtubules in activating Rho GTPases for bacterial internalization.

Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Intracellular Movement of Viruses and Bacteria01:10

Intracellular Movement of Viruses and Bacteria

Intracellular bacteria and viruses often comprise a group of highly infectious pathogens that can cause several diseases. Bacterial pathogens include those belonging to the genus Rickettsia responsible for conditions such as rocky mountain spotted fever and the Mediterranean spotted fever; Chlamydia, a genus responsible for a sexually transmitted disease; Coxiella burnetii, an agent responsible for Q fever. Viral pathogens include vaccinia—a poxvirus, and herpes simplex virus—a virus that...
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...
Microtubule Formation01:23

Microtubule Formation

Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation of...
Cell Polarization by Rho Proteins01:21

Cell 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,...
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...