Integrin trafficking at a glance

Bridgewater, Rebecca E.; Norman, Jim C.; Caswell, Patrick T.

doi:10.1242/jcs.095810

Cited by 172 publications

(181 citation statements)

References 77 publications

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“…At the same time the phosphorylation-dependent regulation of Numb turns this adaptor protein into a molecular switch that links integrin endocytosis to upstream signals involved in cell migration [73]. Endocytosed integrins are transported to early endosomes where sorting into degradative or recycling pathways occurs [70]. While integrins can be routed to degradation, the majority normally recycles rapidly to the cell surface.…”

Section: Integrin Traffickingmentioning

confidence: 99%

“…The decision between degradation and recycling is influenced by proteins like sorting nexin 17 which was shown to prevent the lysosomal degradation of b1 integrins by binding within early endosomes to their cytoplasmic tail [74]. For recycling, integrins can employ either the short Rab4-dependent recycling pathway or the long Rab11-and Arf6-dependent recycling loop which transits through the perinuclear recycling compartment [70]. By modulating the internalization and the transport itinerary of integrins, the endocytic trafficking machinery can influence the composition of focal adhesions which in turn determines cell migration parameters like directionality.…”

Section: Integrin Traffickingmentioning

confidence: 99%

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On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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Directed cell migration is a fundamental process underlying diverse physiological and pathophysiological phenomena ranging from wound healing and induction of immune responses to cancer metastasis. Recent advances reveal that endocytic trafficking contributes to cell migration in multiple ways. (1) At the level of chemokines and chemokine receptors: internalization of chemokines by scavenger receptors is essential for shaping chemotactic gradients in tissue, whereas endocytosis of chemokine receptors and their subsequent recycling is key for maintaining a high responsiveness of migrating cells. (2) At the level of integrin trafficking and focal adhesion dynamics: endosomal pathways do not only modulate adhesion by delivering integrins to their site of action, but also by supplying factors for focal adhesion disassembly. (3) At the level of extracellular matrix reorganization: endosomal transport contributes to tumor cell migration not only by targeting integrins to invadosomes but also by delivering membrane type 1 matrix metalloprotease to the leading edge facilitating proteolysis-dependent chemotaxis. Consequently, numerous endocytic and endosomal factors have been shown to modulate cell migration. In fact key modulators of endocytic trafficking turn out to be also key regulators of cell migration. This review will highlight the recent progress in unraveling the contribution of cellular trafficking pathways to cell migration.

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Section: Integrin Traffickingmentioning

confidence: 99%

Section: Integrin Traffickingmentioning

confidence: 99%

On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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“…This and the notion that FA turnover is strongly dependent on vesicle trafficking and integrin delivery (Bridgewater et al, 2012), led us to ask, whether and how reggies might affect FA turnover and integrin trafficking and recycling.…”

Section: Role Of Rac1 Activationmentioning

confidence: 99%

“…FAs are subject of constant remodeling and turnover (Bridgewater et al, 2012). To determine whether the turnover Quantification of the cell size after 2 h of spreading (n = 3, ** p < 0.01, paired t-test, error bars, SEM).…”

Section: Reggie-1 Downregulation Affects the Turnover Of Fasmentioning

confidence: 99%

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Reggie-1/Flotillin-2 regulates integrin trafficking and focal adhesion turnover via Rab11a

Hülsbusch

Solis

Katanaev

et al. 2015

European Journal of Cell Biology

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a b s t r a c tReggies/flotillins are implicated in trafficking of membrane proteins to their target sites and in the regulation of the Rab11a-dependent targeted recycling of E-cadherin to adherens junctions (AJs). Here we demonstrate a function of reggies in focal adhesion (FA) formation and ␣5-and ␤1-integrin recycling to FAs. Downregulation of reggie-1 in HeLa and A431 cells by siRNA and shRNA increased the number of FAs, impaired their distribution and modified FA turnover. This was coupled to enhanced focal adhesion kinase (FAK) and Rac1 signaling and gain in plasma membrane motility. Wild type and constitutively-active (CA) Rab11a rescued the phenotype (normal number of FAs) whereas dominant-negative (DN) Rab11a mimicked the loss-of-reggie phenotype in control cells. That reggie-1 affects integrin trafficking emerged from the faster loss of internalized antibody-labeled ␤1-integrin in reggie-deficient cells. Moreover, live imaging using TIRF microscopy revealed vesicles containing reggie-1 and ␣5-or ␤1-integrin, trafficking close to the substrate-near membrane and making kiss-and-run contacts with FAs. Thus, reggie-1 in interaction with Rab11a controls Rac1 and FAK activation and coordinates the targeted recycling of ␣5-and ␤1-integrins to FAs to regulate FA formation and membrane dynamics.

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Late endosomal and lysosomal trafficking during integrin‐mediated cell migration and invasion

Rainero

Norman

2013

BioEssays

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Recently it has become clear that trafficking of integrins to late endosomes is key to the regulation of integrin expression and function during cell migration. Here we discuss the molecular machinery that dictates whether integrins are sorted to recycling endosomes or are targeted to late endosomes and lysosomes. Integrins and other receptors that are sorted to late endosomes are not necessarily degraded and, under certain circumstances, can be spared destruction and returned to the cell surface to drive cell migration and invasion. We will discuss 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.

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Integrin trafficking at a glance

Cited by 172 publications

References 77 publications

On the move: endocytic trafficking in cell migration

On the move: endocytic trafficking in cell migration

Reggie-1/Flotillin-2 regulates integrin trafficking and focal adhesion turnover via Rab11a

Late endosomal and lysosomal trafficking during integrin‐mediated cell migration and invasion

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