SNAP-25a and SNAP-25b differently mediate interactions with Munc18-1 and Gβγ subunits
| Autor: | Teresa Daraio, Ismael Valladolid-Acebes, Kerstin Brismar, Christina Bark |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Gene isoform Male Synaptosomal-Associated Protein 25 Immunoprecipitation Vesicle-Associated Membrane Protein 2 Syntaxin 1 Hippocampus Protein–protein interaction 03 medical and health sciences Munc18 Proteins GTP-Binding Proteins Heterotrimeric G protein Animals Protein Isoforms G protein-coupled receptor integumentary system Chemistry General Neuroscience Lipid bilayer fusion Cell biology Mice Inbred C57BL stomatognathic diseases Protein Subunits 030104 developmental biology nervous system SNARE complex |
| Zdroj: | Neuroscience letters. 674 |
| ISSN: | 1872-7972 |
| Popis: | SNAP-25 is a protein involved in regulated membrane fusion and part of the SNARE complex. It exists as two splicing variants, SNAP-25a and SNAP-25b, which differ in 9 out of 206 amino acids. SNAP-25 together with Syntaxin 1 and VAMP-2 forms the ternary SNARE complex essential for mediating activity-dependent release of hormones and neurotransmitters. The functional difference between SNAP-25a and SNAP-25b is poorly understood as both can participate in SNARE complexes and mediate membrane fusion. However, we recently demonstrated that SNAP-25b-deficiency results in metabolic disease and increased insulin secretion. Here we investigated if SNAP-25a and SNAP-25b differently affect interactions with other SNAREs and SNARE-interacting proteins in mouse hippocampus. Adult mice almost exclusively express the SNAP-25b protein in hippocampus whereas SNAP-25b-deficient mice only express SNAP-25a. Immunoprecipitation studies showed no significant differences in amount of Syntaxin 1 and VAMP-2 co-precipitated with the different SNAP-25 isoforms. In contrast, Munc18-1, that preferentially interacts with SNAP-25 via Syntaxin 1 and/or the trimeric SNARE complex, demonstrated an increased ability to bind protein-complexes containing SNAP-25b. Moreover, we found that both SNAP-25 isoforms co-precipitated the Gβγ subunits of the heterotrimeric G proteins, an interaction known to play a role in presynaptic inhibition. We have identified Gβ1 and Gβ2 as the interacting partners of both SNAP-25 isoforms in mouse hippocampus, but Gβ2 was less efficiently captured by SNAP-25a. These results implicate that the two SNAP-25 isoforms could differently mediate protein interactions outside the ternary SNARE core complex and thereby contribute to modulate neurotransmission. |
| Databáze: | OpenAIRE |
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