Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs

Ilaria Cascone, Rasim Selimoglu, Cafer Ozdemir, Elaine Del Nery, Charles Yeaman, Michael White, Jacques Camonis

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

The Ras family G-proteins RalA and RalB make critical non-overlapping contributions to the generation of a tumorigenic regulatory network, supporting bypass of the normal restraints on both cell proliferation and survival. The Sec6/8 complex, or exocyst, has emerged as a principal direct effector complex for Ral GTPases. Here, we show that RalA and RalB support mitotic progression through mobilization of the exocyst for two spatially and kinetically distinct steps of cytokinesis. RalA is required to tether the exocyst to the cytokinetic furrow in early cytokinesis. RalB is then required for recruitment of the exocyst to the midbody of this bridge to drive abscission and completion of cytokinesis. The collaborative action of RalA and RalB is specified by discrete subcellular compartmentalization and unique pairs of RalGEF proteins that provide inputs from both Ras-family protein-dependent and protein-independent regulatory cues. This suggests that Ral GTPases integrate diverse upstream signals to choreograph multiple roles for the exocyst in mitotic progression.

Original languageEnglish (US)
Pages (from-to)2375-2387
Number of pages13
JournalEMBO Journal
Volume27
Issue number18
DOIs
StatePublished - Sep 17 2008

Keywords

  • Cytokinesis
  • Exocyst
  • Ral GTPases
  • RalGEFs

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Cascone, I., Selimoglu, R., Ozdemir, C., Del Nery, E., Yeaman, C., White, M., & Camonis, J. (2008). Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs. EMBO Journal, 27(18), 2375-2387. https://doi.org/10.1038/emboj.2008.166