Delgado Martínez, Ignacio

English

The neuronal SNARE complex, consisting of SNAP-25,            synaptobrevin and syntaxin, is required for presynaptic            exocytosis of neurotransmitter-filled vesicles during            synaptic transmission. However the SNARE complex            undertakes neuronal developmental roles as well.            SNAP-25 has been involved in vesicular fusion during            axonal outgrowth, synaptic formation and trafficking of            glutamate receptors. Its expression is developmentally            regulated by alternative splicing from SNAP-25a to            SNAP-25b. In GABAergic neurons, SNAP-25 seems to be            replaced by SNAP-23, a ubiquitousSNAP-25 homologue,            after synaptogenesis. Deletion of SNAP-25 compromises            neuronal survival in culture, impeding detailed            functional studies. Here, I overcame this difficulty by            reintroducing SNAP-25a, SNAP-25b or SNAP-23 using the            long-term expression lentiviral system in culture            neurons from Snap25 null mice and I was able to dissect            the main functions of SNAP-25. I found that that            SNAP-25 deficient cultured neurons presented impaired            arborization and severe reduction in viability as well            as complete arrest of evoked release and reduction in            the amplitude and frequency of the spontaneous events.            Expression of the SNAP-25 homologues restored neuronal            survival, arborization and the properties of            spontaneous release. In addition, it rescued evoked            release, in both glutamatergic and GABAergic neurons,            although SNAP-23 was found to support exclusively            asynchronous release. SNAP-25b was superior to SNAP-25a            in vesicle priming, which would produce larger            releasable pools after synaptic maturation. My results            revealed SNAP-25 as key component for neuronal survival            and outgrowth, regulation of the synchronous and            asynchronous release and spontaneous activity and            demonstrate a hierarchical ability of the SNAP-25            homologues to support neuronal function

Georg-August-University Göttingen

Functional Studies of SNAP-25 using a knock-out and rescue approach

https://ediss.uni-goettingen.de/bitstream/11858/00-1735-0000-0006-B363-0/1/delgado.pdf

Functional Studies of SNAP-25 using a knock-out and rescue approach

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Georg-August-University Göttingen