RGD Reference Report - Crucial role of the hydrophobic pocket region of Munc18 protein in mast cell degranulation. - Rat Genome Database
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Crucial role of the hydrophobic pocket region of Munc18 protein in mast cell degranulation.

Authors: Bin, Na-Ryum  Jung, Chang Hun  Piggott, Christopher  Sugita, Shuzo 
Citation: Bin NR, etal., Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4610-5. doi: 10.1073/pnas.1214887110. Epub 2013 Mar 4.
RGD ID: 12904029
Pubmed: (View Article at PubMed) PMID:23487749
DOI: Full-text: DOI:10.1073/pnas.1214887110

The function of the Munc18-1 protein hydrophobic pocket, which interacts with the syntaxin-1 N-terminal peptide, has been highly controversial in neurosecretion. Recent analysis of patients with familial hemophagocytic lymphohistiocytosis type 5 has identified the E132A mutation in the hydrophobic pocket of Munc18-2, prompting us to examine the role of this region in the context of immune cell secretion. Double knockdown of Munc18-1 and Munc18-2 in RBL-2H3 mast cells eliminates both IgE-dependent and ionomycin-induced degranulation and causes a significant reduction in syntaxin-11 without altering expressions of the other syntaxin isoforms examined. These phenotypes were effectively rescued on reexpression of wild-type Munc18-1 or Munc18-2 but not the mutants (F115E, E132A, and F115E/E132A) in the hydrophobic pocket of Munc18. In addition, these mutants show that they are unable to directly interact with syntaxin-11, as tested through protein interaction experiments. Our results demonstrate the crucial roles of the hydrophobic pocket of Munc18 in mast cell degranulation, which include the regulation of syntaxin-11. We also suggest that the functional importance of this region is significantly different between neuronal and immune cell exocytosis.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Stxbp1  (syntaxin binding protein 1)
Stxbp2  (syntaxin binding protein 2)


Additional Information