Functional specialization of the yeast Rho1 GTP exchange factors

Krause, S. , Cundell, M., Poon, P., McGhie, J., Johnston, G., Price, C. and Gray, J. (2012) Functional specialization of the yeast Rho1 GTP exchange factors. Journal of Cell Science, 125(11), pp. 2721-2731. (doi: 10.1242/​jcs.100685) (PMID:22344253)

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Abstract

Rho GTPases are regulated in complex spatiotemporal patterns that may be dependent, in part at least, on the multiplicity of their GTP exchange factors (GEFs). Here, we examine the extent of and basis for functional specialization of the Rom2 and Tus1 GEFs that activate the yeast Rho1 GTPase, the ortholog of mammalian RhoA. First, we find that these GEFs selectively activate different Rho1-effector branches. Second, the synthetic genetic networks around ROM2 and TUS1 confirm very different global in vivo roles for these GEFs. Third, the GEFs are not functionally interchangeable: Tus1 cannot replace the essential role of Rom2, even when overexpressed. Fourth, we find that Rom2 and Tus1 localize differently: Rom2 to the growing bud surface and to the bud neck at cytokinesis; Tus1 only to the bud neck but in a distinct pattern. Finally, we find that these GEFs are dependent on different protein co-factors: Rom2 function and localization is largely dependent on Ack1, a SEL1 domain containing protein; Tus1 function and localization is largely dependent on the Tus1-interacting protein Ypl066w (which we name Rgl1). We have revealed a surprising level of diversity among the Rho1 GEFs that contributes another level of complexity to the spatiotemporal control of Rho1.

Item Type:Articles
Keywords:RHO1, GTP exchange factor, Cytokinesis, ROM2, TUS1
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Krause, Dr Sue and Gray, Professor Joseph and McGhie, Mrs Josephine
Authors: Krause, S., Cundell, M., Poon, P., McGhie, J., Johnston, G., Price, C., and Gray, J.
Subjects:Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH345 Biochemistry
Q Science > QH Natural history > QH426 Genetics
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Research Group:Joseph V Gray, School of Life Sciences, MVLS
Journal Name:Journal of Cell Science
ISSN:0021-9533
ISSN (Online):1477-9137
Published Online:17 February 2012
Copyright Holders:Copyright © 2012 The Company of Biologists Ltd.
First Published:First published in Journal of Cell Science 2012 125(11):2721-2731
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438341Analysis of the structure, function and regulation of the Rho1-specific GTP exchange proteins in the yeast call wall integrity pathwayJoseph GrayBiotechnology and Biological Sciences Research Council (BBSRC)BB/E011632/1LS - BIOMOLECULAR SCIENCE