RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling

Nagaraj Balasubramanian, Jeremy A. Meier, David W. Scott, Andrés Norambuena, Michael A. White, Martin Alexander Schwartz

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Anchorage dependence of cell growth is a key metastasis-suppression mechanism that is mediated by effects of integrins on growth signaling pathways [1]. The small GTPase RalA is activated in metastatic cancers through multiple mechanisms and specifically induces anchorage independence [2-4]. Loss of integrin-mediated adhesion triggers caveolin-dependent internalization of cholesterol- and sphingolipid-rich lipid raft microdomains to the recycling endosomes; these domains serve as platforms for many signaling pathways, and their clearance from the plasma membrane (PM) after cell detachment suppresses growth signaling [5, 6]. Conversely, readhesion triggers their return to the PM and restores growth signaling. Activation of Arf6 by integrins mediates exit of raft markers from the recycling endosomes but is not sufficient for return to the PM. We now show that RalA but not RalB mediates integrin-dependent membrane raft exocytosis through the exocyst complex. Constitutively active RalA restores membrane raft targeting to promote anchorage-independent growth signaling. Ras-transformed pancreatic cancer cells also show RalA-dependent constitutive PM raft targeting. These results identify RalA as a key determinant of integrin-dependent membrane raft trafficking and regulation of growth signaling. They therefore define a mechanism by which RalA regulates anchorage dependence and provide a new link between integrin signaling and cancer.

Original languageEnglish (US)
Pages (from-to)75-79
Number of pages5
JournalCurrent Biology
Volume20
Issue number1
DOIs
StatePublished - Jan 12 2010

Fingerprint

exocytosis
integrins
Exocytosis
Integrins
Membranes
Cell membranes
plasma membrane
Growth
Cell Membrane
endosomes
Endosomes
recycling
Recycling
Caveolins
pancreatic neoplasms
sphingolipids
Sphingolipids
neoplasms
Monomeric GTP-Binding Proteins
guanosinetriphosphatase

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling. / Balasubramanian, Nagaraj; Meier, Jeremy A.; Scott, David W.; Norambuena, Andrés; White, Michael A.; Schwartz, Martin Alexander.

In: Current Biology, Vol. 20, No. 1, 12.01.2010, p. 75-79.

Research output: Contribution to journalArticle

Balasubramanian, N, Meier, JA, Scott, DW, Norambuena, A, White, MA & Schwartz, MA 2010, 'RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling', Current Biology, vol. 20, no. 1, pp. 75-79. https://doi.org/10.1016/j.cub.2009.11.016
Balasubramanian, Nagaraj ; Meier, Jeremy A. ; Scott, David W. ; Norambuena, Andrés ; White, Michael A. ; Schwartz, Martin Alexander. / RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling. In: Current Biology. 2010 ; Vol. 20, No. 1. pp. 75-79.
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