Publications by authors named "Girish H Kedar"
Unlabelled: Munc18-1 is essential for vesicle fusion and participates in the docking of large dense-core vesicles to the plasma membrane. Recent structural data suggest that conformational changes in the 12th helix of the Munc18-1 domain 3a within the Munc18-1:syntaxin complex result in an additional interaction with synaptobrevin-2/VAMP2 (vesicle-associated membrane protein 2), leading to SNARE complex formation. To test this hypothesis in living cells, we examined secretion from Munc18-1-null mouse adrenal chromaffin cells expressing Munc18-1 mutants designed to either perturb the extension of helix 12 (Δ324-339), block its interaction with synaptobrevin-2 (L348R), or extend the helix to promote coil-coil interactions with other proteins (P335A).
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- - Synaptotagmin-1 (Syt1) is crucial for vesicle docking and fusion in chromaffin cells, with its C2B domain interacting with specific membrane proteins and lipids.
- - A double mutation in Syt1 (R398/399Q) was found to restore docking ability in Syt1-null cells, but this process depended on a certain lipid (PI(4,5)P2); however, it did not restore secretion or fusion capabilities.
- - The study reveals that distinct regions of the C2B domain in Syt1 play different roles in docking versus triggering vesicle fusion, highlighting the complexity of the mechanisms involved.