title: Rac1 and RhoA: Networks, loops and bistability.
abstract: Cell migration requires a precise temporal and spatial coordination of several processes which allow the cell to efficiently move. The extension and retraction of membrane protrusion, as well as adhesion are controlled by the Rho-family small GTPases. Two members of the family, Rac1 and RhoA, can show opposite behaviors and spatial localisations, with RhoA being active toward the rear of the cell and regulating its retraction during migration, whereas Rac1 is active toward the front of the cell. In addition to the spatial segregation, RhoA and Rac1 activity at the leading edge of the cells has an element of temporal segregation, with RhoA and Rac1 activities peaking at separate points during the migratory cycle of protrusion and retraction. Elements of this separation have been explained by the presence of 2 mutually inhibitory feedbacks, where Rac1 inhibits RhoA and RhoA in turn can inhibit Rac1. Recently, it was shown that Rac1 and RhoA activity and downstream signaling respond in a bistable manner to perturbations of this network.
authors.affiliation: a Department of Biochemistry and Molecular Biology , Biomedicine Discovery Institute, Monash University , Melbourne , Victoria , Australia.
authors.forename: Lan K
authors.initials: LK
authors.lastname: Nguyen
authors.affiliation: b Systems Biology Ireland , University College Dublin , Belfield , Dublin , Ireland.|c Conway Institute, University College Dublin , Belfield , Dublin , Ireland.|d School of Medicine and Medical Science, University College Dublin , Belfield , Dublin , Ireland.
authors.forename: Boris N
authors.initials: BN
authors.lastname: Kholodenko
authors.affiliation: e Edinburgh Cancer Research Center , IGMM, University of Edinburgh , Edinburgh , UK.
authors.forename: Alex
authors.initials: A
authors.lastname: von Kriegsheim
mesh_terms: D000818:Animals; D004795:Enzyme Stability; D006801:Humans; D020830:rac1 GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: PAK inhibition; Rac1; RhoA; bistable switches; cell motility; mathematical modeling