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Phosphorylation of PACSIN2 by protein kinase C triggers the removal of caveolae from the plasma membrane

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Item Type:Article
Title:Phosphorylation of PACSIN2 by protein kinase C triggers the removal of caveolae from the plasma membrane
Creators Name:Senju, Y. and Rosenbaum, E. and Shah, C. and Hamada-Nakahara, S. and Itoh, Y. and Yamamoto, K. and Hanawa-Suetsugu, K. and Daumke, O. and Suetsugu, S.
Abstract:PACSIN2, a membrane-sculpting BAR domain protein, localizes to caveolae. Here, we found that protein kinase C (PKC) phosphorylates PACSIN2 at serine 313, thereby decreasing its membrane binding and tubulation capacities. Concomitantly, phosphorylation decreased the time span for which caveolae could be tracked at the plasma membrane (the ‘tracking duration’). Analyses of the phospho-mimetic S313E mutant suggested that PACSIN2 phosphorylation was sufficient to reduce caveolar-tracking durations. Both hypotonic treatment and isotonic drug-induced PKC activation increased PACSIN2 phosphorylation at serine 313 and shortened caveolar-tracking durations. Caveolar-tracking durations were also reduced upon the expression of other membrane-binding-deficient PACSIN2 mutants or upon RNA interference (RNAi)-mediated PACSIN2 depletion, pointing to a role for PACSIN2 levels in modulating the lifetime of caveolae. Interestingly, the decrease in membrane-bound PACSIN2 was inversely correlated with the recruitment and activity of dynamin 2, a GTPase that mediates membrane scission. Furthermore, expression of EHD2, which stabilizes caveolae and binds to PACSIN2, restored the tracking durations of cells with reduced PACSIN2 levels. These findings suggest that the PACSIN2 phosphorylation decreases its membrane-binding activity, thereby decreasing its stabilizing effect on caveolae and triggering dynamin-mediated removal of caveolae.
Keywords:Caveolae, BAR Domain, Phosphorylation, Protein Kinase C, Mechanical Stress
Source:Journal of Cell Science
Publisher:Company of Biologists
Page Range:2766-2780
Date:1 August 2015
Additional Information:Copyright © 2015 The Authors. Published by The Company of Biologists Ltd.
Official Publication:https://doi.org/10.1242/jcs.167775
PubMed:View item in PubMed

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