Related Experiment Video
Updated: Oct 27, 2025
06:42
Author Spotlight: Understanding Disease Mechanisms Through Real-Time Analysis of T-Cell Migration
Published on: May 24, 2024
1.8K
Intracellular nanovesicles mediate α5β1 integrin trafficking during cell migration.
Gabrielle Larocque1, Daniel J Moore1, Méghane Sittewelle1
1Centre for Mechanochemical Cell Biology, Warwick Medical School, Coventry, UK.
The Journal of Cell Biology
|July 21, 2021
Summary
Tumor protein D54 (TPD54) and related proteins regulate cell migration by influencing intracellular nanovesicles (INVs) and integrin recycling. Their manipulation impacts cancer metastasis and cell motility.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Membrane traffic, including endocytosis and recycling of cell surface receptors like integrins, is crucial for cell migration.
- Intracellular nanovesicles (INVs) are key players in membrane trafficking, and tumor protein D54 (TPD54) is the sole known marker for INVs.
- Overexpression of TPD52-like proteins in cancer correlates with poor prognosis and metastasis, suggesting a role in altered cell migration.
Purpose of the Study:
- To investigate the role of TPD54 and TPD52-like proteins in membrane trafficking and cell migration.
- To elucidate the mechanism by which TPD54 associates with INVs.
- To determine the impact of TPD52-like proteins on cancer cell motility and invasion.
Main Methods:
- Biochemical assays to demonstrate TPD54 binding to membranes and association with INVs.
- Identification of the TPD54 motif responsible for INV association.
- Analysis of the Rab GTPase complement of INVs.
- Functional studies involving depletion or overexpression of TPD52-like proteins to assess effects on cell migration and invasion.
- Investigation of α5β1 integrin recycling.
Main Results:
- TPD54 directly binds to membranes and associates with INVs through a C-terminal charged motif.
- Other TPD52-like proteins also associate with INVs, which contain a specific Rab GTPase complement.
- Depletion of TPD52-like proteins significantly inhibits cell migration and invasion.
- Overexpression of TPD52-like proteins enhances cell motility.
- Altered recycling of α5β1 integrins within INVs is implicated in the inhibition of migration.
Conclusions:
- TPD52-like proteins, including TPD54, are critical regulators of membrane traffic and cell migration via INVs.
- These proteins influence cell motility and invasion, potentially through modulation of integrin recycling.
- The findings highlight TPD52-like proteins as potential therapeutic targets for modulating cancer metastasis.
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
3.1K
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...
Some...
3.1K
01:15Activation of Integrins
4.1K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
4.1K
01:32Cytoskeletal Coordination in Cell Migration
5.1K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
5.1K
01:10Integrins
4.5K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.5K
01:09Cell Migration
17.5K
Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
17.5K
01:19Cell Migration
5.5K
Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
5.5K