RABGTPases in MT1-MMP trafficking and cell invasion: Physiology versus pathology

Stefan Linder1, Giorgio Scita

  • 1a Institute for Medical Microbiology; Virology and Hygiene ; University Medical Center Eppendorf ; Hamburg , Germany.

Small Gtpases
|June 25, 2015
PubMed

Insights

Matrix metalloproteinase MT1-MMP regulates cell invasion. RABGTPases, particularly RAB5a, are crucial for MT1-MMP cell surface transport in macrophages and cancer cells, impacting health and disease.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Matrix metalloproteinase MT1-MMP is vital for cell invasion in physiological and pathological processes.
  • MT1-MMP modifies the cell surface and pericellular environment by cleaving various proteins.
  • Pathways controlling MT1-MMP cell surface exposure remain largely unelucidated.

Purpose of the Study:

  • To investigate the role of RABGTPases in regulating MT1-MMP trafficking.
  • To compare MT1-MMP trafficking pathways in primary human macrophages and carcinoma cells.
  • To identify commonalities and differences in RABGTPase-dependent MT1-MMP transport.

Main Methods:

  • Utilized primary human macrophages and carcinoma cell lines.
  • Investigated the function of specific RABGTPases, including RAB5a.
  • Analyzed the trafficking of MT1-MMP in relation to RABGTPase activity.

Main Results:

  • A subset of RABGTPases, notably RAB5a, was identified as critical for MT1-MMP trafficking.
  • Common and distinct RABGTPase-dependent trafficking mechanisms were observed in macrophages and carcinoma cells.
  • Findings highlight the importance of RABGTPases in controlling MT1-MMP cell surface presentation.

Conclusions:

  • RABGTPases play a key role in regulating MT1-MMP cell surface exposure.
  • Understanding these pathways offers insights into cell invasion in both normal and diseased states.
  • This research provides a foundation for exploring therapeutic strategies targeting MT1-MMP-mediated invasion.

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:
5.7K
Rab Cascades01:25

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
3.8K
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,...
10.3K
GTPases and their Regulation02:14

GTPases and their Regulation

3.3K
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,...
4.1K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.8K