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

Yosuke Senju, Eva Rosenbaum, Claudio Shah, Sayaka Hamada-Nakahara, Yuzuru Itoh, Kimiko Yamamoto, Kyoko Hanawa-Suetsugu, Oliver Daumke, Shiro Suetsugu

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 caveolartracking durations. Both hypotonic treatment and isotonic druginduced PKC activation increased PACSIN2 phosphorylation at serine 313 and shortened caveolar-tracking durations. Caveolartracking 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 dynaminmediated removal of caveolae.

Original languageEnglish
Pages (from-to)2766-2780
Number of pages15
JournalJournal of cell science
Volume128
Issue number15
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Keywords

  • BAR domain
  • Caveolae
  • Mechanical stress
  • Phosphorylation
  • Protein kinase C

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Senju, Y., Rosenbaum, E., Shah, C., Hamada-Nakahara, S., Itoh, Y., Yamamoto, K., Hanawa-Suetsugu, K., Daumke, O., & Suetsugu, S. (2015). Phosphorylation of PACSIN2 by protein kinase C triggers the removal of caveolae from the plasma membrane. Journal of cell science, 128(15), 2766-2780. https://doi.org/10.1242/jcs.167775