AI Article Synopsis
- - Membrane fusion, crucial for processes like synaptic transmission, relies on the assembly of SNARE complexes, driven by various proteins that facilitate their formation.
- - This study highlights the essential roles of NSF (a AAA+ protein) and SNAP in preparing syntaxin clusters before fusion, indicating their involvement in maintaining SNARE protein quality and organization.
- - By using cryo-EM, researchers detailed how NSF and SNAP interact with syntaxin, revealing that sequential ATP hydrolysis is vital for the disassembly of SNARE complexes, suggesting these clusters act as reservoirs for efficient fusion.
Article Abstract
Membrane fusion is driven by SNARE complex formation across cellular contexts, including vesicle fusion during synaptic transmission. Multiple proteins organize trans-SNARE complex assembly and priming, leading to fusion. One target membrane SNARE, syntaxin, forms nanodomains at the active zone, and another, SNAP-25, enters non-fusogenic complexes with it. Here, we show that the AAA+ protein NSF (N-ethylmaleimide sensitive factor) and SNAP (soluble NSF attachment protein) must act prior to fusion. We show that syntaxin clusters are conserved, that NSF colocalizes with them, and characterize SNARE populations within and near these clusters using cryo-EM. Supercomplexes of NSF, α-SNAP, and either a syntaxin tetramer or two binary complexes of syntaxin-SNAP-25 reveal atomic details of SNARE processing and show how sequential ATP hydrolysis drives disassembly. These results suggest a functional role for syntaxin clusters as reservoirs and a corresponding role for NSF in syntaxin liberation and SNARE protein quality control preceding fusion.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482947 | PMC |
| http://dx.doi.org/10.1101/2024.10.11.617886 | DOI Listing |
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