A likely role for the PH-domain containing protein, PEPP2/ PLEKHA5, at the membrane-microtubule cytoskeleton interface

PH(pleckstrin homology)domains are well known to bind membrane phosphoinositides with different specificities and direct PH domain-containing proteins to discrete subcellular compartments with assistances of alternative binding partners.PH domain-containing proteins have been found to be involved in a wide range of cellular events,including signalling,cytoskeleton rearrangement and vesicular trafficking.Here we showed that a novel PH domain-containing protein,PEPP2(also known as PLEKHA5),displays moderate phosphoinositide binding specificity.Full length PEPP2 was observed to variably associate with both the plasma membrane and microtubules.The membrane-associated PEPP2 nucleated at cell-cell contacts and the leading edge of migrating cells.Overexpression of PEPP2 increased membrane microviscosity,indicating a potential role for PEPP2 in regulating function of microtubule-dependent membrane functions.