Neuronal SNARE complex assembly guided by Munc18‐1 and Munc13‐1

Abstract

Neurotransmitter release by Ca2+‐triggered synaptic vesicle exocytosis is essential for information transmission in the nervous system. The soluble N‐ethylmaleimide sensitive factor attachment protein receptors (SNAREs) syntaxin‐1, SNAP‐25, and synaptobrevin‐2 form the SNARE complex to bring synaptic vesicles and the plasma membranes together and to catalyze membrane fusion. Munc18‐1 and Munc13‐1 regulate synaptic vesicle priming via orchestrating neuronal SNARE complex assembly. In this review, we summarize recent advances toward the functions and molecular mechanisms of Munc18‐1 and Munc13‐1 in guiding neuronal SNARE complex assembly, and discuss the functional similarities and differences between Munc18‐1 and Munc13‐1 in neurons and their homologs in other intracellular membrane trafficking systems.

Role of GARP Vesicle Tethering Complex in Golgi Physiology

“…The exact nature of the GARP–SNARE interaction is not known, but it was shown that the assembled GARP complex could bind to the assembled STX16 SNARE complex [ 28 ]. It is important to note that the VPS53 protein contains a MUN structural domain [ 33 ] and that the founding member of the MUN family, Munc13-1, binds to both SNAREs and SNARE-interacting SM (Sec1/Munc18) proteins regulating the transition from Munc18-syntaxin-1 pre-fusion complex to a fusogenic trans -SNARE complex during synaptic vesicle fusion [ 34 ].…”

Innovation and renovation: FEBS Open Bio in 2023

“…Our final In the Limelight issue of 2022 focussed on neurotransmitter release: guest editor Josep Rizo and co‐authors kicked off the issue by discussing the important role that structural biology has played in uncovering the mechanisms underlying neurotransmitter release while highlighting the limitations of this approach [ 13 ]. In the second review article in the issue, Frédéric Pincet and co‐authors used experimental data and simple physics and chemistry models to analyse the kinetics and energetics of the entire fusion process [ 14 ]. Concluding the issue, Shen Wang and Cong Ma described the current understanding of how the Munc18‐1 and Munc13‐1 proteins guide neuronal SNARE complex assembly [ 15 ].…”

Exploring the conformational changes of the Munc18‐1/syntaxin 1a complex

“…SNARE proteins form a larger protein family that catalyzes the fusion of various types of transport vesicles in eukaryotic cells. Several other conserved proteins ensure that the SNARE proteins are tightly regulated, including the Rab proteins, Sec1/Munc18‐like (SM) proteins, and a group of tethering proteins known as complex associated with tethering containing helical rods (CATCHR) proteins (Jahn & Fasshauer, 2012 ; Rizo, 2022 ; Stanton & Hughson, 2023 ; Südhof & Rothman, 2009 ; Wang & Ma, 2022 ).…”

“…The fact that two different mutations at different sites of the complex can lead to overall similar effects suggests that syntaxin‐1a remains bound to Munc18‐1 and that a conformational switch within the complex might explain role of Munc18‐1 in promoting SNARE complex assembly (Burkhardt et al, 2008 ; Colbert et al, 2013 ) The idea that SM proteins could guide SNARE complex assembly was suspected early on (Misura et al, 2000 ), but supporting data were slow to come to light (Baker et al, 2015 ; Burkhardt et al, 2008 ). Indeed, it is currently thought that Munc18‐1 catalyzes the formation of a SNARE complex by providing an assembly platform for the three SNARE proteins (Rizo, 2022 ; Stanton & Hughson, 2023 ; Wang & Ma, 2022 ). Slowly, a clearer picture is emerging, but there are still many unanswered questions.…”