Interplay between Rab35 and Arf6 controls cargo recycling to coordinate cell adhesion and migration
Patrick D. Allaire,Mohamed Seyed Sadr,Mathilde Chaineau,Emad Seyed Sadr,Sarah Konefal,Maryam Fotouhi,Deborah Maret,Brigitte Ritter,Rolando F. Del Maestro,Peter S. McPherson +9 more
TL;DR: It is demonstrated that the small GTPase Rab35 maintains cadherins at the cell surface to promote cell–cell adhesion and that Rab35 expression is suppressed in a subset of cancers characterized by Arf6 hyperactivity.
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Abstract: Cells inversely adjust the plasma membrane levels of integrins and cadherins during cell migration and cell-cell adhesion but the regulatory mechanisms that coordinate these trafficking events remain unknown. Here, we demonstrate that the small GTPase Rab35 maintains cadherins at the cell surface to promote cell-cell adhesion. Simultaneously, Rab35 supresses the activity of the GTPase Arf6 to downregulate an Arf6-dependent recycling pathway for β1-integrin and EGF receptors, resulting in inhibition of cell migration and attenuation of signaling downstream of these receptors. Importantly, the phenotypes of decreased cell adhesion and increased cell migration observed following Rab35 knock down are consistent with the epithelial-mesenchymal transition, a feature of invasive cancer cells, and we show that Rab35 expression is suppressed in a subset of cancers characterized by Arf6 hyperactivity. Our data thus identify a key molecular mechanism that efficiently coordinates the inverse intracellular sorting and cell surface levels of cadherin and integrin receptors for cell migration and differentiation.
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References
A tubular EHD1-containing compartment involved in the recycling of major histocompatibility complex class I molecules to the plasma membrane.
Steve Caplan,Naava Naslavsky,Lisa M. Hartnell,Robert Lodge,Roman S. Polishchuk,Julie G. Donaldson,Juan S. Bonifacino +6 more
TL;DR: It is reported that endogenous EHD proteins, as well as transgenic tagged EHD1, are associated with long, membrane‐bound tubules containing Arf6, and observations suggest an additional function of E HD1 as a tubule‐inducing factor in the Arf 6 pathway for recycling of plasma membrane proteins internalized by clathrin‐independent endocytosis.
ARF6 is required for growth factor- and rac-mediated membrane ruffling in macrophages at a stage distal to rac membrane targeting.
TL;DR: Data demonstrate that intact ARF6 function is required for coupling activated Rac to one of several effector pathways and suggest that a principal function of ARf6 is to coordinate Rac activation with plasma membrane-based protrusive events.
Activation of ARF6 by ARNO stimulates epithelial cell migration through downstream activation of both Rac1 and phospholipase D
TL;DR: It is suggested that ARF6 activation stimulates two distinct signaling pathways, one leading to Rac activation, the other to changes in membrane phospholipid composition, and that both pathways are required for cell motility.
Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets.
TL;DR: This study provides the first genetic evidence that tyrosine phosphorylation of pp125FAK is dependent on integrin- mediated events, and demonstrates that there is a strong correlation between tyrosines phosphorylated in platelets, and the activation of pp 125FAK-associated phosphorylating activity in vitro.
EFA6A enhances glioma cell invasion through ADP ribosylation factor 6/extracellular signal-regulated kinase signaling.
Ming Li,Samuel Sai Ming Ng,Jide Wang,Lihui Lai,Suet Yi Leung,Michel Franco,Ying Peng,Ming-Liang He,Hsiang-Fu Kung,Marie Chia Mi Lin +9 more
TL;DR: It is suggested for the first time a potential role of EFA6A/ARF6/ERK signal cascade in glioma cell migration and invasion and in wound healing and in vitro cell invasion assays.