Review
Regulation of membrane traffic by integrin signaling

https://doi.org/10.1016/j.tcb.2011.02.003Get rights and content

Membrane trafficking pathways function to sort and transport cargoes to various intracellular compartments and to the plasma membrane. This allows precise spatiotemporal control of processes such as signal transduction, which in turn is crucial for complex cell functions such as cell division, migration and polarity. Recent studies identified cell–matrix adhesions as regulators of exocytosis, endocytosis and the recycling machinery, thus establishing a new layer of crosstalk between cell adhesion and signaling. This review discusses these findings and considers their implications for signaling events downstream of integrins and growth factor receptors.

Section snippets

Protein sorting and distribution

Precise regulation of the distribution of proteins and signaling activities within a cell is required for all biological processes, ranging from asymmetric division of stem cells to epithelial cell polarity and planar cell polarity within a tissue. The sorting and distribution of proteins requires the integration of several cellular machineries. First, intrinsic protein sorting signals regulate the partitioning of proteins to various lipid compartments. This occurs at three major sites, the

Integrin regulation of plasma membrane order

The lipid bilayer of the plasma membrane is highly asymmetric, and this asymmetrical organization is crucial for cell physiology. The most obvious example is the organization of the plasma membrane of polarized cells into apical and basolateral macrodomains with distinct lipid compositions. Plasma membranes are further subcompartmentalized into lipid rafts, which are dynamic, highly ordered, nanoscale assemblies enriched in sphingolipids, cholesterol and glycosylphosphatidylinositol

Integrin signaling and endocytosis

Lipid rafts function as plasma membrane scaffolds and as regulators of endocytosis. This function has been studied extensively in the context of caveolae, a specialized subtype of lipid rafts. Caveolae are flask-shaped plasma membrane invaginations that are found in almost all mammalian cell types. In addition to their characteristic morphology, caveolae can be identified by the presence of their main structural component, the intramembrane protein caveolin-1 [19]. Several features distinguish

Integrin signaling and exocytosis

Integrins can also control the secretion of soluble and membrane-associated proteins including growth factors such as transforming growth factor β (TGF-β), VEGF and insulin 48, 49, 50, and proteases such as matrix metalloproteinase-2 [51], which represents an additional mechanism for controlling important cellular activities. While mechanistic insights into how integrins control these processes are still largely lacking, mechanisms underlying integrin-mediated targeted delivery of proteins to

Concluding remarks

It has become clear that adhesion signaling exerts part of its effect on cellular behavior through the regulation of membrane traffic. Future studies will reveal the relative importance of this mode of regulation in respect to other mechanisms of integrin signaling, such as the direct activation of signaling pathways. In addition, the exact molecular details of this regulation require further experimental attention. Sufficient evidence exists to conclude that the regulation of endo- and

Acknowledgements

We thank Roy Zent for comments on the manuscript. Work in the Wickström and Fässler laboratories is supported by the Max Planck Society.

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