TY - JOUR

T1 - Functional specialisation of yeast Rho1 GTP exchange factors

AU - Krause, Sue Ann

AU - Cundell, Michael J.

AU - Poon, Pak P.

AU - McGhie, Josephine

AU - Johnston, Gerry C.

AU - Price, Clive

AU - Gray, Joseph V.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Rho GTPases are regulated in complex spatiotemporal patterns that might 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 specialisation of the Rom2 and Tus1 GEFs that activate the yeast Rho1 GTPase, the orthologue 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 localise 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 localisation is largely dependent on Ack1, a SEL1-domain-containing protein; Tus1 function and localisation 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.

AB - Rho GTPases are regulated in complex spatiotemporal patterns that might 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 specialisation of the Rom2 and Tus1 GEFs that activate the yeast Rho1 GTPase, the orthologue 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 localise 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 localisation is largely dependent on Ack1, a SEL1-domain-containing protein; Tus1 function and localisation 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.

KW - Guanosine Triphosphate

KW - Guanine Nucleotide Exchange Factors

KW - Saccharomyces cerevisiae Proteins

KW - Gene Regulatory Networks

KW - rho GTP-Binding Proteins

KW - Time Factors

KW - Mutation

KW - Signal Transduction

KW - Saccharomyces cerevisiae

KW - Protein Transport

UR - http://www.scopus.com/inward/record.url?scp=84864976352&partnerID=8YFLogxK

U2 - 10.1242/jcs.100685

DO - 10.1242/jcs.100685

M3 - Journal article

C2 - 22344253

VL - 125

SP - 2721

EP - 2731

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 1477-9137

IS - 11

ER -