The function of VAMP2 in mediating membrane fusion: An overview

Abstract

Vesicle-associated membrane protein 2 (VAMP2, also known as synaptobrevin-2), encoded by VAMP2 in humans, is a key component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. VAMP2 combined with syntaxin-1A (SYX-1A) and synaptosome-associated protein 25 (SNAP-25) produces a force that induces the formation of fusion pores, thereby mediating the fusion of synaptic vesicles and the release of neurotransmitters. VAMP2 is largely unstructured in the absence of interaction partners. Upon interaction with other SNAREs, the structure of VAMP2 stabilizes, resulting in the formation of four structural domains. In this review, we highlight the current knowledge of the roles of the VAMP2 domains and the interaction between VAMP2 and various fusion-related proteins in the presynaptic cytoplasm during the fusion process. Our summary will contribute to a better understanding of the roles of the VAMP2 protein in membrane fusion.

Proteome Profiling of Rat Brain Cortical Changes during Early Postnatal Brain Development

“…In addition to the aforementioned key regulatory components of the membrane fusion SNARE complex, the Vesicle-Fusing ATPase (NSF), Alpha-synuclein (SNCA), and Vesicle-associated membrane proteins (VAMP1, VAMP2, VAMP3, VAMP4, VAMP7, and VAMP8) were also part of the complex (ref and the references therein), with VAMP2 being the most prominent. Accordingly, these proteins demonstrated similar rising PND expression profiles.…”

Age-induced midbrain-striatum assembloids model early phenotypes of Parkinson’s disease

“…Dysregulation of synaptic and DA neurotransmission pathways revealed in the transcriptomic data of Progerin-overexpressing assembloids, was further validated by the downregulation of the post-synaptic protein Gephyrin, an important scaffolding protein that regulates the organisation of post-synapses in striatal GABAergic neurons (Choii & Ko, 2015), and the pre-synaptic proteins VAMP2 and Synaptotagmin1. VAMP2 regulates the fusion of synaptic vesicles and neurotransmitter release through the SNARE complex (Yan et al, 2022) and Synaptotagmin1 is an essential Ca 2+ sensor for the fast release of DA (Banerjee et al, 2020, 2022). In parallel, catecholamine measurements showed significantly lower catecholamine levels in the striatum of the Progerin-overexpressing assembloids, indicating dysregulation of DA release in the aged-induced model, a PD-relevant phenotype (Jiang et al, 2019).…”

Advancements in the study of synaptic plasticity and mitochondrial autophagy relationship

“…alpha-synuclein (α-Syn), soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) protein family, Rab proteins, and they participate in physiological processes such as neurotransmitter release and synaptic plasticity. These proteins play essential roles in regulating neurotransmitter release and various aspects of synaptic plasticity (Fouke et al, 2021;Gao et al, 2023;Somasundaram & Taraska, 2018;Sun et al, 2019;Yan, Jiang, et al, 2022) (Corradi et al, 2013). On the other hand, the deletion of SYN III gene results in behavioral flexibility deficits observed in some psychiatric disorders (Moore et al, 2021) (Figure 1b).…”

“…The members of the synaptic vesicle‐associated protein family primarily include synaptophysin (SYN), synaptic vesicle 2 (SV2), vesicle‐associated membrane protein (VAMP), synaptotagmin (SYT), alpha‐synuclein (α‐Syn), soluble N‐ethylmaleimide‐sensitive factor attachment receptor (SNARE) protein family, Rab proteins, and they participate in physiological processes such as neurotransmitter release and synaptic plasticity. These proteins play essential roles in regulating neurotransmitter release and various aspects of synaptic plasticity (Fouke et al., 2021; Gao et al., 2023; Somasundaram & Taraska, 2018; Sun et al., 2019; Yan, Jiang, et al., 2022) (Table 2).…”