Regulated internalization and recycling of integrin receptors is crucial for the modulating cell adhesion and migration, but the molecular mechanisms underlying these processes are poorly understood. Two new studies identify key proteins involved in 1 integrin re-insertion to the plasma membrane.

Upon internalization from the plasma membrane, proteins and membranes are transported to the early endosome where they are sorted for degradation or recycling. In Dev. Cell, Li et al. report that the direct association of ACAP1, a GTPase-activating protein, with endosomal 1 integrin is necessary for 1 recycling. Moreover, they show that phosphorylation of ACAP1 at Ser554 by Akt regulates the ACAP11 integrin interaction in endosomes. Given that Akt is activated by various growth and survival factors, Akt could be important for the regulation of 1 integrin recycling in response to extracellular signals.

Downregulation of either ACAP1 or Akt by siRNA inhibited HeLA cell migration on fibronectin and in wound healing assays. Interestingly, ACAP1 was recently found to bind to transferrin receptors and promote their transport from the recycling endosome to the plasma membrane. This study suggests that ACAP1 could have a more general role in sorting receptor recycling.

PKC has also been shown to regulate integrin recycling to the plasma membrane. In another study in EMBO, Ivaska et al. identify the intermediate filament vimentin as a PKC phosphorylation target in vesicles containing in PKC/1 integrin in vitro. Inhibition of PKC prevented the release of a vimentin-PKC complex from vesicles suggesting that PKC-mediated phosphorylation of vimentin is required to dissociate vesicles from intermediate filaments and aid their return to the plasma membrane. In agreement with these findings, vimentin was found to promote cell motility in a PKC dependent manner, but the consequences of vimentin phosphorylation on integrin recycling are yet to be examined.

Thus, by aiding protein sorting and vesicle release from the cytoskeleton, Akt and PKC seem to aid 1 integrin recycling and cell motility. As new regulators of the 1 integrin recycling are discovered, it will be interesting to elucidate how they integrate extracellular signals and coordinate their activities during cell migration.

Author: Monica Hoyos-Flight