Integrin Trafficking and the Control of Cell Migration

  title={Integrin Trafficking and the Control of Cell Migration},
  author={Patrick T. Caswell and Jim C. Norman},
In the late 1980s and early 1990s, the observation that certain integrin heterodimers are continually internalized from the plasma membrane into endosomal compartments and subsequently recycled back to the cell surface indicated that the endocytic and recycling pathways have the potential to exert minute‐to‐minute control over integrin function. This insight has prompted others to study the regulation of integrin trafficking in more detail. This review aims to summarize the findings of studies… 

Endocytic Trafficking of Integrins in Cell Migration

Integrin traffic

Mechanistic insight is provided into how integrin traffic is regulated in cells by controlling small GTPases or stabilizing cytoskeletal tracks that are crucial for efficient traffic of integrins to the plasma membrane.

Integrins: masters and slaves of endocytic transport

New findings indicate that integrin trafficking dictates the nature of Rho GTPase signalling during cytokinesis and cell migration and can exert control over the trafficking of other receptors in a way that drives cancer cell invasion and tumour angiogenesis.

Quantitative Analysis of Integrin Trafficking.

This chapter will focus on quantitative approaches based on cell surface biotinylation and capture ELISA to measure endocytosis, recycling, and cell surface levels of integrin receptors.

Trafficking and Cell Migration

Taken together, endocytosis enables migrating cells and tissues to dynamically modulate their adhesion and signalling, allowing them to efficiently migrate through their extracellular environment.

Persistent cell migration and adhesion rely on retrograde transport of β1 integrin

It is demonstrated that β1 integrin (known as PAT-3 in Caenorhabditis elegans), but not β3, is transported from the plasma membrane to the trans-Golgi network, to be resecreted in a polarized manner.

Late endosomal and lysosomal trafficking during integrin-mediated cell migration and invasion: cell matrix receptors are trafficked through the late endosomal pathway in a way that dictates how cells migrate.

  • E. RaineroJ. Norman
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2013
How the exchange of adhesion receptors and other key regulators of cell migration between late endosomes/lysosomes and the plasma membrane can promote dynamic turnover of adhesions during cell migration is discussed.

Distinct Recycling of Active and Inactive β1 Integrins

The endocytic trafficking of active and inactive β1 integrins in cancer cells is investigated and the possibility of a previously unappreciated crosstalk between pathways regulating integrin activity and traffic is implied.

Endocytosis and spatial restriction of cell signaling




Endocytosis and recycling of the fibronectin receptor in CHO cells.

It is shown that an anti‐fibronectin receptor monoclonal antibody preferentially labels the leading edges of freshly plated CHO fibroblasts, suggesting that this receptor circulates through the endocytic cycle, and establishes that the processes of endocytosis/exocyTosis and cell locomotion are intimately linked.

Stimulation‐Dependent Recycling of Integrin β1 Regulated by ARF6 and Rab11

In comparison to the internalization pathways of endocytosis, the recycling pathways are less understood. Even less defined is the process of regulated recycling, as few examples exist and their

In migrating fibroblasts, recycling receptors are concentrated in narrow tubules in the pericentriolar area, and then routed to the plasma membrane of the leading lamella

By following the intracellular processing of recycling transferrin receptors and the selective sorting of a-2 macroglobulin in chick embryo fibroblasts, we have shown that the concentration of 60 nm

PKCϵ controls the traffic of β1 integrins in motile cells

The evidence presented indicates that PKCϵ controls an internal traffic step that under uninhibited conditions permits the recycling of β1 integrin, contributing to cell motility.

PDGF-regulated rab4-dependent recycling of alphavbeta3 integrin from early endosomes is necessary for cell adhesion and spreading.

It is proposed that growth factor-regulated, rab4-dependent recycling of alphavbeta3 integrin from early endosomes to the plasma membrane is a critical upstream event in the assembly of cell-matrix contacts.

Migrating fibroblasts perform polarized, microtubule-dependent exocytosis towards the leading edge

It is concluded that microtubules are necessary for the domain-specific fusion of post-Golgi vesicles with the plasma membrane during migration.

A tyrosine‐based sorting signal in the β2 integrin cytoplasmic domain mediates its recycling to the plasma membrane and is required for ligand‐supported migration

Both of these mutants display a severe impairment in ligand‐supported migration, suggesting the existence in integrin cytoplasmic domains of independent signals regulating apparently unrelated functions that are required to sustain cell migration over specific ligands.

Urokinase receptor and integrin interactions.

In vivo data reveal altered integrin function and cell migration when u PAR:integrin interactions are impaired, supporting the idea that uPAR:Integrin interactions may be a focal point of intervention in pathobiology whereIntegrin function is crucial, such as tumor metastasis.