The dynamic behaviour of cellular protrusions in polarised cell regions is important for cell migration and morphogenesis, and requires a balanced membrane turnover by endocytosis. The small GTPase Rab8 has been shown to regulate polarised trafficking that enables protrusion formation, and, Richard Lundmark and colleagues now (p. 1147) investigate how the activity of Rab8 is coordinated with vesicular trafficking during compensatory endocytosis. They show here that Rab8 is endocytosed from cell protrusions by GTPase regulator associated with focal adhesion kinase-1 (GRAF1) via clathrin-independent endocytosis (CLIC), resulting in its removal from the cell surface. Accordingly, GRAF1-depleted cells exhibit increased levels of Rab8 at protrusions and are unable to spread, indicating that a restriction of Rab8 activity at protrusions is required for their dynamic turnover. Furthermore, by altering the osmolarity of the medium, the authors demonstrate that reduced membrane tension induces the recruitment of Rab8 and mediates its internalisation by CLIC, whereas under conditions of high membrane tension, endocytosis is inhibited and Rab8 associates with exocytic vesicles. On the basis of these findings, the authors propose that endocytic turnover and inactivation of Rab8 by GRAF1-mediated CLIC is important for balancing membrane redistribution between growing and retracting regions of the cell, thus maintaining the overall cell polarity.
