Affiliation:
1. Department of Functional Genomics and Clinical Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit (VU) Amsterdam and VU Medical Center, de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
Abstract
Neuronal dense-core vesicles (DCVs) transport and secrete neuropeptides necessary for development, plasticity and survival, but little is known about their fusion mechanism. We show that Snap-25 null mutant (SNAP-25 KO) neurons, previously shown to degenerate after 4 days in vitro (DIV), contain fewer DCVs and have reduced DCV fusion probability in surviving neurons at DIV14. At DIV3, before degeneration, SNAP-25 KO neurons show normal DCV fusion, but one day later fusion is significantly reduced. To test if other SNAP homologs support DCV fusion, we expressed SNAP-23, -29 or -47 in SNAP-25 KO neurons. SNAP-23 and -29 rescued viability and supported DCV fusion in SNAP-25 KO neurons, but SNAP-23 more efficiently. SNAP-23 also rescued synaptic vesicle (SV) fusion while SNAP-29 did not. SNAP-47 failed to rescue viability and did not support DCV or SV fusion. These data demonstrate a developmental switch, in hippocampal neurons between DIV3-4, where DCV fusion becomes SNAP-25 dependent. Furthermore, SNAP-25 homologs support DCV and SV fusion and neuronal viability to a variable extent, SNAP-23 most effectively, SNAP-29 less so and SNAP-47 ineffective.
Funder
European Research Council
Publisher
The Company of Biologists
Cited by
39 articles.
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