Reconstitution of the Vital Functions of Munc18 and Munc13 in Neurotransmitter Release

TLDR

Synaptic vesicle fusion has been reconstituted in vitro, but prior systems lacked key proteins such as Munc18‑1 and Munc13, preventing explanation of their essential role in neurotransmitter release. The study demonstrates that membrane fusion requires both Munc18‑1 and Munc13 when all eight essential components are included.

Abstract

Reconstituting Synaptic Vesicle Fusion Membrane fusion reactions have been reconstituted in vitro, but often the reconstituted reactions have not directly mirrored the requirements for synaptic vesicle fusion in vivo. Previous work generally used only N -ethylmaleimide–sensitive factor (NSF) attachment protein SNAP receptors (SNAREs) and one or two additional components and could not explain why deletion of Munc18-1 or Munc13 abolishes neurotransmitter release completely, yielding the severe disruptions of synaptic vesicle release in knockout mouse. Ma et al. (p. 421 , published online 20 December; see the Perspective by Hughson ) now present a faithful reconstitution of synaptic vesicle fusion. Membrane fusion required Munc18-1 and Munc13 when the reconstitution experiments included all eight key components (three SNAREs, Munc18-1, Munc13, synaptotagmin-1, NSF, and α-SNAP).