SNARE-Mediated Exocytosis in Neuronal Development

Abstract

The formation of the nervous system involves establishing complex networks of synaptic connections between proper partners. This developmental undertaking requires the rapid expansion of the plasma membrane surface area as neurons grow and polarize, extending axons through the extracellular environment. Critical to the expansion of the plasma membrane and addition of plasma membrane material is exocytic vesicle fusion, a regulated mechanism driven by soluble N-ethylmaleimide-sensitive factor attachment proteins receptors (SNAREs). Since their discovery, SNAREs have been implicated in several critical neuronal functions involving exocytic fusion in addition to synaptic transmission, including neurite initiation and outgrowth, axon specification, axon extension, and synaptogenesis. Decades of research have uncovered a rich variety of SNARE expression and function. The basis of SNARE-mediated fusion, the opening of a fusion pore, remains an enigmatic event, despite an incredible amount of research, as fusion is not only heterogeneous but also spatially small and temporally fast. Multiple modes of exocytosis have been proposed, with full-vesicle fusion (FFV) and kiss-and-run (KNR) being the best described. Whereas most in vitro work has reconstituted fusion using VAMP-2, SNAP-25, and syntaxin-1; there is much to learn regarding the behaviors of distinct SNARE complexes. In the past few years, robust heterogeneity in the kinetics and fate of the fusion pore that varies by cell type have been uncovered, suggesting a paradigm shift in how the modes of exocytosis are viewed is warranted. Here, we explore both classic and recent work uncovering the variety of SNAREs and their importance in the development of neurons, as well as historical and newly proposed modes of exocytosis, their regulation, and proteins involved in the regulation of fusion kinetics.

Immunohistochemical distribution of proteins involved in glutamate release in subepithelial sensory nerve endings of rat epiglottis

“…On the other hand, syntaxin 1A, syntaxin 1B, and syntaxin 3 are expressed in presynaptic membranes in the brain (Cupertino et al 2016). In the present study, SNAP25 and syntaxin 1 may be expressed in laryngeal nerve endings; however, it remains unclear whether the syntaxin 1 antibody used in the present Regarding v-SNARE proteins, VAMP1, VAMP2, VAMP3, VAMP4, and VAMP7 are expressed in brain tissue, and VAMP2 is brain-enriched (Urbina and Gupton 2020). Previous studies demonstrated that VAMP2 was distributed in rat carotid sinus baroreceptors (Yokoyama et al 2020), but not in the periodontal Ruffini endings of rat incisors (Honma et al 2010).…”

Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control

“…Snap25 is an important component of the soluble N-ethylmaleimide-sensitive factor attachment protein (SNARE) complex, contributes formation of 2 out of 4 α helices of the complex, and regulates the membrane fusion during the process of exocytosis ( 29 ). The SNARE-mediated fusion such as exocytic fusion and synaptic transmission involved vesicle-associated membrane protein-2 (VAMP2), SNAP25, and syntaxin-1, which are sufficient to fuse membranes in vitro experiments ( 30 ). Snap25 is developmentally regulated in neuroendocrine cells and SNAP25a precedes SNAP25b in the development of mouse brain, and SNAP25b becomes major splicing variant at the 2 nd postnatal week ( 31 ).…”

TRIM67 regulates exocytic mode and neuronal morphogenesis via SNAP47

“…VAMP2 is the most highly expressed vesicle (v)-SNARE during neuronal development ( Cardoso-Moreira et al, 2019 ; La Manno et al, 2016 ; Urbina and Gupton, 2020 ) and is present on recycling vesicles and post-Golgi vesicles ( Figures S1A and S1B ). VAMP2-pHluorin-labeled exocytic events in embryonic murine cortical neurons were imaged at 2 days in vitro (2 DIV) by total internal reflection fluorescence (TIRF) microscopy.…”