Avidity-driven polarity establishment via multivalent anionic lipid-Cdc42 module interactions

RDP seminar by Derek McCusker from IECB - IBGC (Bordeaux, France)

Abstract
While Rho GTPases are indispensible regulators of cellular polarity, the mechanisms responsible for their site-specific activation at membranes during polarity axis establishment require identification. Using the budding yeast Cdc42 GTPase module, which is composed of an activating Guanine nucleotide Exchange Factor (GEF) and the scaffold Bem1, we uncover avidity via multivalent anionic lipid interactions as a critical mechanistic constituent of polarity establishment. We identify a Cationic- enriched Lipid Interacting Cluster (CLIC) sequence in the N-terminus of Bem1 that is necessary to drive the recruitment of Bem1, and with it the Cdc42 GEF, to anionic lipids enriched at the cell pole. The CLIC sequence extensively penetrates anionic lipid bilayers, rigidifying and shaping the local lipid environment. Moreover, when appended to a lipid-binding defective cdc42 mutant, the affinity of the Bem1 CLIC sequence for anionic lipids is sufficient to target cdc42 to the plasma membrane and support viability. The CLIC and PX sequences in Bem1 function in parallel to a PH domain in the Cdc42 GEF. This system illustrates the importance of avidity via multivalent anionic lipid interactions in the spatio-temporal control of Rho GTPase activity.

Date : Monday, January 15th
Time : 11.00-12.00
Location : Salle des Thèses

Selected publications
– Scaffold-mediated gating of Cdc42 signalling flux.
Rapali P, Mitteau R, Braun C, Massoni-Laporte A, Ünlü C, Bataille L, Arramon FS, Gygi SP, McCusker D.​ ​
Elife. 2017 Mar 17 ;6. pii : e25257. doi : 10.7554/eLife.25257.
– Bub3-BubR1-dependent sequestration of Cdc20Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes.​ ​
Derive N, Landmann C, Montembault E, Claverie MC, Pierre-Elies P, Goutte-Gattat D, Founounou N, McCusker D.​ ​
J Cell Biol. 2015 Nov 9 ;211(3):517-32. doi : 10.1083/jcb.201504059.
– A quantitative imaging-based screen reveals the exocyst as a network hub connecting endocytosis and exocytosis.​ ​
Jose M, Tollis S, Nair D, Mitteau R, Velours C, Massoni-Laporte A, Royou A, Sibarita JB, McCusker D.​ ​
Mol Biol Cell. 2015 Jul 1 ;26(13):2519-34. doi : 10.1091/mbc.E14-11-1527. Epub 2015 May 6.
– Robust polarity establishment occurs via an endocytosis-based cortical corralling mechanism.​ ​
Jose M, Tollis S, Nair D, Sibarita JB, McCusker D.​ ​
J Cell Biol. 2013 Feb 18 ;200(4):407-18. doi : 10.1083/jcb.201206081. Epub 2013 Feb 11.

RDP host : Yvon Jaillais