Login / Signup

Allosteric regulation of exocyst: Discrete activation of tethering by two spatial signals.

Brittany K MillerGuendalina RossiSara HudsonDavid CullyRichard W BakerPatrick J Brennwald
Published in: The Journal of cell biology (2023)
The exocyst imparts spatial control during exocytic vesicle tethering through its interactions with proteins and lipids on the vesicle and the plasma membrane. One such interaction is with the vesicle tether Sro7, although the outcome of this interaction is poorly understood. Here, we describe how Sro7 binding to the Exo84 subunit results in activation of the exocyst complex which leads to an increase in avidity for the Rab GTPase Sec4 and an increase in exocyst-mediated vesicle tethering. Gain-of-function (GOF) mutations in Exo84 that mimic Sro7 activation replicate these biochemical changes and result in allosteric changes within the complex. Direct comparison of GOF mutants which mimic Sro7- and Rho/Cdc42-activation of the exocyst reveals distinct mechanisms and outcomes. We propose a model by which these two activation pathways reside within the same tethering complex but remain insulated from one another. Structural modeling suggests a related mechanism for Sro7 activation of the exocyst in yeast and Ral GTPase activation of the exocyst in animal cells.
Keyphrases
  • small molecule
  • type diabetes
  • induced apoptosis
  • cell death
  • cell cycle
  • saccharomyces cerevisiae
  • glycemic control