Rac1 and RhoA: Networks, loops and bistability

Lan K. Nguyen, Boris N. Kholodenko, Alex von Kriegsheim

Research output: Contribution to journalArticleOtherpeer-review

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)316-321
Number of pages6
JournalSmall GTPases
Volume9
Issue number4
DOIs
Publication statusPublished - 2018

Keywords

  • bistable switches
  • cell motility
  • mathematical modeling
  • PAK inhibition
  • Rac1
  • RhoA

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