Sphingosine 1-phosphate induces filopodia formation through S1PR2 activation of ERM proteins

K. Alexa Orr Gandy, Daniel Canals, Mohamad Adada, Masayuki Wada, Patrick Roddy, Ashley J. Snider, Yusuf A. Hannun, Lina M. Obeid

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Previously we demonstrated that the sphingolipids ceramide and S1P (sphingosine 1-phosphate) regulate phosphorylation of the ERM (ezrin/radixin/moesin) family of cytoskeletal proteins [Canals, Jenkins, Roddy,Hernande-Corbacho, Obeid and Hannun (2010) J. Biol. Chem. 285, 32476-3285]. In the present article,we show that exogenously applied or endogenously generated S1P (in a sphingosine kinase-dependent manner) results in significant increases in phosphorylation of ERM proteins as well as filopodia formation. Using phosphomimetic and non-phosphorylatable ezrin mutants, we show that the S1P-induced cytoskeletal protrusions are dependent on ERM phosphorylation. Employing various pharmacological S1PR (S1P receptor) agonists and antagonists, along with siRNA(small interfering RNA) techniques and genetic knockout approaches, we identify the S1PR2 as the specific and necessary receptor to induce phosphorylation of ERM proteins and subsequent filopodia formation. Taken together, the results demonstrate a novel mechanism by which S1P regulates cellular architecture that requires S1PR2 and subsequent phosphorylation of ERM proteins.

Original languageEnglish (US)
Pages (from-to)661-672
Number of pages12
JournalBiochemical Journal
Volume449
Issue number3
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Keywords

  • ERM phosphorylation
  • Ezrin/radixin/moesin (ERM)
  • Filopodia formation
  • Scaffolding protein
  • Sphingosine 1-phosphate receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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