PKC kicks PACSIN2 out of caveolae

Caveolae-localised PACSIN2 [protein kinase C (PKC) and casein kinase substrate in neurons] contains an F-BAR domain, which sculpts membranes into tubules, and SH3 and linker domains, which mediate binding to other proteins. Drosophila PACSIN and mammalian PASCIN1 and PACSIN2 can be phosphorylated at the linker region, but the kinase responsible and the effects of the phosphorylation on membrane binding are unknown. In this issue (p. 2766), Shiro Suetsugu and colleagues conducted a detailed investigation that uncovered a mechanistic link between PKC, PACSIN2 and caveolar dynamics. They found that PACSIN2 was phosphorylated by PKC at serine 313, and that this phosphorylation was increased during hypotonic and shear stresses. Although the phosphorylation did not affect PACSIN2 dimerization or its interaction with other known binding partners, it decreased PACSIN2-mediated membrane tubulation. Caveolae tracking revealed that a long-lived caveolae fraction was decreased upon hypotonic stress, PACSIN2 knockdown, PKC activation and when membrane binding or phospho-mimetic PACSIN2 mutants were expressed. Furthermore, the authors present data suggesting that dynamin promotes the removal of phosphorylated PACSIN2 from the caveolar membrane. In summary, this study presents novel findings that support a model in which activated PKC phosphorylates PACSIN2, which disrupts its membrane association, thereby facilitating dynamin-dependent scission and increasing caveolar dynamics.