The deubiquitylase USP33 discriminates between RALB functions in autophagy and innate immune response

Abstract

The RAS-like GTPase RALB mediates cellular responses to nutrient availability or viral infection by respectively engaging two components of the exocyst complex, EXO84 and SEC5. RALB employs SEC5 to trigger innate immunity signalling, whereas RALB-EXO84 interaction induces autophagocytosis. How this differential interaction is achieved molecularly by the RAL GTPase remains unknown. We found that whereas GTP binding turns on RALB activity, ubiquitylation of RALB at Lys 47 tunes its activity towards a particular effector. Specifically, ubiquitylation at Lys 47 sterically inhibits RALB binding to EXO84, while facilitating its interaction with SEC5. Double-stranded RNA promotes RALB ubiquitylation and SEC5-TBK1 complex formation. In contrast, nutrient starvation induces RALB deubiquitylation by accumulation and relocalization of the deubiquitylase USP33 to RALB-positive vesicles. Deubiquitylated RALB promotes the assembly of the RALB-EXO84-beclin-1 complexes driving autophagosome formation. Thus, ubiquitylation within the effector-binding domain provides the switch for the dual functions of RALB in autophagy and innate immune responses.

Phytophthora infestans RXLR effector AVR1 interacts with exocyst component Sec5 to manipulate plant immunity

“…Sec5 was found to participate in Toll-like receptor-mediated innate immune signaling by interacting with and activating TANK-BINDING KINASE1 (Chien et al, 2006;Ishikawa and Barber, 2008;Simicek et al, 2013). Our data suggest a similar multifunctional role for Sec5 in plants.…”

RNA silencing of exocyst genes in the stigma impairs the acceptance of compatible pollen in Arabidopsis

“…7). Distinct roles are beginning to be identified for subsets of exocyst subunits such as EXO84 and SEC5 in autophagy and innate immunity signaling in mammalian cells (Bodemann et al, 2011;Simicek et al, 2013). SEC5 and EXO84, along with EXO70B1, have also been linked to autophagy in Arabidopsis .…”

The Exocyst at a Glance

“…In addition, the RalB-Exo84 complex was shown to interact with beclin-1 to regulate autophagosome assembly in response to starvation (Bodemann et al, 2011). The switch of RalB binding from Exo84 to Sec5 is mediated by ubiquitylation of RalB (Simicek et al, 2013). It is interesting to note that the exocyst mostly plays a role as a signaling scaffold in the above mentioned process.…”

“…Recent studies have shown different subcellular localizations of these two sub-complexes, and suggested their involvement in different cellular functions, such as autophagy and innate immunity (Bodemann et al, 2011). Furthermore, ubiquitylation of RalB promotes the switch from an interaction between RalB, Exo84 and beclin1 to that beteen RalB, Sec5 and TBK1, which further differentiates the roles of Ral and the exocyst in different processes (Simicek et al, 2013).…”