Dataset Information

Coro1a promotes the multivesicular body and plasma membrane fusion by facilitating PKM2-mediated SNAP-23 phosphorylation

ABSTRACT: During the formation of endosomal pathway-dependent extracellular vesicles (EVs), intraluminal vesicles in multivesicular bodies (MVBs) fuse with the plasma membrane (PM), releasing intraluminal vesicles to produce exosomes. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, membrane fusion effector, is essential in this process. However, which SNARE complex is involved in MVB and PM fusion and how its assembly is regulated remain elusive. We have demonstrated that neddylation of Coro1a inhibits EV secretion by inducing Rab7-mediated degradation of MVBs. Here, we find that Coro1a increases EV biogenesis by promoting the assembly of SNARE complex STX-12-SNAP-23-VAMP-7 in a neddylation-independent manner.

ORGANISM(S): Homo Sapiens

SUBMITTER: Zhijian Cai

PROVIDER: PXD071700 | iProX | Sun Dec 07 00:00:00 GMT 2025

REPOSITORIES: iProX

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Publications

Coro1a promotes the multivesicular body and plasma membrane fusion by facilitating PKM2-mediated SNAP-23 phosphorylation.

Cai Zhenzhai Z Li Zhijie Z Li Nannan N He Xinyu X Jin Yang Y Lin Daopo D Fu Beilei B Ma Xingjian X Hong Dongzhi D Lin Kezhi K Wu Hao H

Communications biology 20260609

The release of exosomes involves the fusion of multivesicular bodies (MVBs) with the plasma membrane (PM), a process driven by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. However, the specific SNARE complex mediating MVB-PM fusion and its regulatory mechanism remain unclear. Here, we show that Coronin-1a (Coro1a) increases extracellular vesicle (EV) biogenesis by promoting the assembly of the STX-12-SNAP-23-VAMP-7 SNARE complex independent of neddyl ...[more]

PMID: 42265296

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Project description:Extracellular vesicles (EVs) are small membrane-derived vesicles that shuttle proteins or nucleic acids between glia and neurons, thereby promoting neuronal survival and plasticity in the CNS. Exosomes are small EVs (40-150 nm) that are derived from multi-vesicular bodies (MVBs) of the endo-lysosomal pathway, formed by inward budding of the limiting membrane into the MVB lumen and released into the extracellular space upon fusion of the MVB with the plasma membrane (PM). Previous research revealed certain effector molecules to be required for exosome release. For instance, RAB GTPases have been shown to control exosome release in a cell- and tissue-specific manner. In addition, exosome release appears to be evoked by membrane depolarization in conjunction with calcium influx and to depend on members of the SNARE family of proteins. However, the specific cellular and molecular factors that regulate neuronal exosome release and segregate it from the release of neurotransmitter vesicles are currently unknown. Here, we used a combination of molecular biology, patch-clamp electrophysiology and pH-sensitive dye imaging to examine the effect of the neuronal growth and differentiation factors basic fibroblast growth factor (bFGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) on neuronal EV release. We found that bFGF-treatment of cultured hippocampal neurons increased the abundance of EVs in the culture medium as measured by Western blot and nanoparticle tracking analysis (NTA), without affecting the number or size of neuronal MVBs. The effect of bFGF depended on calcium and on receptor tyrosine kinase (RTK) activity as the calcium chelating agent BAPTA and the tyrosine kinase inhibitor genistein both abolished the bFGF-induced increase in EV release. In accord with these results, untreated neurons had a low rate of spontaneous and stimulus-evoked MVB-PM fusion events as measured by pH-sensitive dye imaging in conjunction with patch-clamp electrophysiology, but treatment with bFGF significantly increased the number of neurons exhibiting MVB-PM fusion events in response to a high-frequency stimulus. Proteomic analysis of neuronal EVs by Liquid Chromatography Mass Spectrometry (LC-MS) demonstrated bFGF to increase the abundance of the v-SNARE vesicle-associated membrane protein 3 (VAMP3, cellubrevin) on EVs, whereas VAMP2 was decreased. Conversely, knocking-down VAMP3 in cultured neurons abolished the effect of bFGF on EV release. Similar to bFGF, the classical neurotrophins BDNF and NGF increased neuronal EV release in a VAMP3-dependent manner. In summary, our results thus reveal a new function for neurotrophic factor signalling in controlling neuronal exosome release and support the investigation of growth factor-mediated signal transduction via EVs in the healthy and diseased CNS.

Dataset Information

Coro1a promotes the multivesicular body and plasma membrane fusion by facilitating PKM2-mediated SNAP-23 phosphorylation

Publications

Coro1a promotes the multivesicular body and plasma membrane fusion by facilitating PKM2-mediated SNAP-23 phosphorylation.

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