QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 19, Issue 4, 1404-1414, April 2008

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E07-10-1053v1 19/4/1404    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Belanis, L. Articles by Kloog, Y. Search for Related Content PubMed PubMed Citation Articles by Belanis, L. Articles by Kloog, Y.

Galectin-1 Is a Novel Structural Component and a Major Regulator of H-Ras Nanoclusters

Liron Belanis^*,, Sarah J. Plowman^,, Barak Rotblat^*, John F. Hancock, and Yoel Kloog^*

*Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel; and Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia

Submitted October 19, 2007; Revised December 17, 2007; Accepted January 17, 2008
Monitoring Editor: J. Silvio Gutkind

The organization of Ras proteins into nanoclusters on the inner plasma membrane is essential for Ras signal transduction, but the mechanisms that drive nanoclustering are unknown. Here we show that epidermal growth factor receptor activation stimulates the formation of H-Ras.GTP-Galectin-1 (Gal-1) complexes on the plasma membrane that are then assembled into transient nanoclusters. Gal-1 is therefore an integral structural component of the H-Ras–signaling nanocluster. Increasing Gal-1 levels increases the stability of H-Ras nanoclusters, leading to enhanced effector recruitment and signal output. Elements in the H-Ras C-terminal hypervariable region and an activated G-domain are required for H-Ras–Gal-1 interaction. Palmitoylation is not required for H-Ras–Gal-1 complex formation, but is required to anchor H-Ras–Gal-1 complexes to the plasma membrane. Our data suggest a mechanism for H-Ras nanoclustering that involves a dual role for Gal-1 as a critical scaffolding protein and a molecular chaperone that contributes to H-Ras trafficking by returning depalmitoylated H-Ras to the Golgi complex for repalmitoylation.

These authors contributed equally to this work.

Address correspondence to: Yoel Kloog (kloog{at}post.tau.ac.il) or John F. Hancock (j.hancock{at}imb.uq.edu.au)

Abbreviations used: Gal-1, galectin-1; EGF, epidermal growth factor; HVR, hypervariable region; FLIM-FRET, fluorescence lifetime imaging-fluorescence resonance energy transfer; BiFC, bimolecular fluorescence complementation; mRFP, monomeric red fluorescent protein; mGFP, monomeric green fluorescent protein; YFP, yellow fluorescent protein; YN, N-terminal fragment of YFP; YC, C-terminal fragment of YFP; RBD, Ras-binding domain of Raf-1.

This article has been cited by other articles:

				R. Shalom-Feuerstein, S. J. Plowman, B. Rotblat, N. Ariotti, T. Tian, J. F. Hancock, and Y. Kloog K-Ras Nanoclustering Is Subverted by Overexpression of the Scaffold Protein Galectin-3 Cancer Res., August 15, 2008; 68(16): 6608 - 6616. [Abstract] [Full Text] [PDF]

				S. Yalovsky, D. Bloch, N. Sorek, and B. Kost Regulation of Membrane Trafficking, Cytoskeleton Dynamics, and Cell Polarity by ROP/RAC GTPases Plant Physiology, August 1, 2008; 147(4): 1527 - 1543. [Full Text] [PDF]