title: Functional specialisation of yeast Rho1 GTP exchange factors.
abstract: 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.
authors.affiliation: School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Sue Ann
authors.initials: SA
authors.lastname: Krause
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cundell
authors.forename: Pak P
authors.initials: PP
authors.lastname: Poon
authors.forename: Josephine
authors.initials: J
authors.lastname: McGhie
authors.forename: Gerry C
authors.initials: GC
authors.lastname: Johnston
authors.forename: Clive
authors.initials: C
authors.lastname: Price
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Gray
mesh_terms: D053263:Gene Regulatory Networks / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C490929:ROM2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C448998:TUS1 protein, S cerevisiae; D006160:Guanosine Triphosphate; C051302:RHO1 protein, S cerevisiae; D020741:rho GTP-Binding Proteins