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Munc18-1 promotes large dense-core vesicle docking
T Voets1, R F Toonen, E C Brian
1Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany. thomas.voets@med.kuleven.ac.be
Neuron
|September 8, 2001
Summary
Munc18-1 is crucial for secretory vesicle docking and calcium-triggered exocytosis. Its absence severely impairs large dense-core vesicle (LDCV) secretion and docking in chromaffin cells.
Area of Science:
- Cell Biology
- Neuroscience
- Biochemistry
Background:
- Secretory vesicles must dock at the plasma membrane for calcium-triggered exocytosis.
- SNARE complex assembly (Synaptobrevin, Syntaxin-1, SNAP-25) is essential for exocytosis.
- Munc18-1 is a known cytosolic binding partner of Syntaxin-1.
Purpose of the Study:
- To investigate the role of Munc18-1 in large dense-core vesicle (LDCV) secretion.
- To determine Munc18-1's function in the exocytosis pathway.
Main Methods:
- Analysis of Munc18-1 function in mouse chromaffin cells lacking the protein.
- Studying calcium-dependent LDCV exocytosis and vesicle docking.
- Investigating the effects of Munc18-1 overexpression in bovine chromaffin cells.
Main Results:
- Munc18-1 deficiency caused a 10-fold reduction in calcium-dependent LDCV exocytosis.
- Mutant cells showed a 10-fold decrease in morphologically docked LDCVs.
- Munc18-1 overexpression enhanced releasable vesicle pools and accelerated supply.
Conclusions:
- Munc18-1 plays a critical role upstream of SNARE complex formation.
- Munc18-1 is essential for promoting LDCV docking at the plasma membrane.
- Munc18-1 is a key regulator of regulated exocytosis.