The syntaxin 4 N terminus regulates its basolateral targeting by munc18c-dependent and -independent mechanisms
| Autor: | Mirjam M. P. Zegers, Jacqueline Torres, Holly M. Funk, Martin B.A. ter Beest |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Munc18 Proteins
endocrine system Vesicle fusion Mutation Missense Biology medicine.disease_cause Biochemistry environment and public health Exocytosis Dogs Protein targeting medicine Syntaxin Animals Molecular Biology Membrane transport and intracellular motility Translational research [NCMLS 5] Protein Stability Qa-SNARE Proteins urogenital system Cell Membrane Basolateral plasma membrane Cell Biology Syntaxin 3 Cell biology Transport protein Protein Transport nervous system biological phenomena cell phenomena and immunity Peptides SNARE Proteins Protein Binding |
| Zdroj: | Journal of Biological Chemistry, 286, 10834-46 Journal of Biological Chemistry, 286, 12, pp. 10834-46 |
| ISSN: | 0021-9258 |
| Popis: | Contains fulltext : 97454.pdf (Publisher’s version ) (Open Access) To generate and maintain epithelial cell polarity, specific sorting of proteins into vesicles destined for the apical and basolateral domain is required. Syntaxin 3 and 4 are apical and basolateral SNARE proteins important for the specificity of vesicle fusion at the apical and basolateral plasma membrane domains, respectively, but how these proteins are specifically targeted to these domains themselves is unclear. Munc18/SM proteins are potential regulators of this process. Like syntaxins, they are crucial for exocytosis and vesicle fusion. However, how munc18c and syntaxin 4 regulate the function of each other is unclear. Here, we investigated the requirement of syntaxin 4 in the delivery of basolateral membrane and secretory proteins, the basolateral targeting of syntaxin 4, and the role of munc18c in this targeting. Depletion of syntaxin 4 resulted in significant reduction of basolateral targeting, suggesting no compensation by other syntaxin forms. Mutational analysis identified amino acids Leu-25 and to a lesser extent Val-26 as essential for correct localization of syntaxin 4. Recently, it was shown that the N-terminal peptide of syntaxin 4 is involved in binding to munc18c. A mutation in this region that affects munc18c binding shows that munc18c binding is required for stabilization of syntaxin 4 at the plasma membrane but not for its correct targeting. We conclude that the N terminus serves two functions in membrane targeting. First, it harbors the sorting motif, which targets syntaxin 4 basolaterally in a munc18c-independent manner and second, it allows for munc18c binding, which stabilizes the protein in a munc18c-dependent manner. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|