Revisiting interaction specificity reveals neuronal and adipocyte Munc18 membrane fusion regulatory proteins differ in their binding interactions with partner SNARE Syntaxins
| Autor: | Andrew E. Whitten, Asma Rehman, Shu-Hong Hu, Jennifer L. Martin, Gordon J. King, Michelle P. Christie, Brett M. Collins, Russell Jarrott |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glycerol Munc18 Proteins Cell Membranes lcsh:Medicine Plasma protein binding Monomers (Chemistry) Biology Biochemistry Membrane Fusion 03 medical and health sciences Adipocytes Syntaxin Protease Inhibitors Polymer chemistry Vesicles Enzyme Inhibitors lcsh:Science Protein Interactions Ternary complex Imidazole Binding selectivity Neurons Multidisciplinary VAMP2 Organic Compounds Qa-SNARE Proteins lcsh:R Organic Chemistry Chemical Compounds SNAP25 Lipid bilayer fusion Biology and Life Sciences Membrane Proteins Proteins Cell Biology Cell biology Physical sciences Chemistry 030104 developmental biology Enzymology lcsh:Q biological phenomena cell phenomena and immunity Cellular Structures and Organelles SNARE Proteins Research Article Protein Binding |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 10, p e0187302 (2017) |
| ISSN: | 1932-6203 |
| Popis: | The efficient delivery of cellular cargo relies on the fusion of cargo-carrying vesicles with the correct membrane at the correct time. These spatiotemporal fusion events occur when SNARE proteins on the vesicle interact with cognate SNARE proteins on the target membrane. Regulatory Munc18 proteins are thought to contribute to SNARE interaction specificity through interaction with the SNARE protein Syntaxin. Neuronal Munc18a interacts with Syntaxin1 but not Syntaxin4, and adipocyte Munc18c interacts with Syntaxin4 but not Syntaxin1. Here we show that this accepted view of specificity needs revision. We find that Munc18c interacts with both Syntaxin4 and Syntaxin1, and appears to bind "non-cognate" Syntaxin1 a little more tightly than Syntaxin4. Munc18a binds Syntaxin1 and Syntaxin4, though it interacts with its cognate Syntaxin1 much more tightly. We also observed that when bound to non-cognate Munc18c, Syntaxin1 captures its neuronal SNARE partners SNAP25 and VAMP2, and Munc18c can bind to pre-formed neuronal SNARE ternary complex. These findings reveal that Munc18a and Munc18c bind Syntaxins differently. Munc18c relies principally on the Syntaxin N-peptide interaction for binding Syntaxin4 or Syntaxin1, whereas Munc18a can bind Syntaxin1 tightly whether or not the Syntaxin1 N-peptide is present. We conclude that Munc18a and Munc18c differ in their binding interactions with Syntaxins: Munc18a has two tight binding modes/sites for Syntaxins as defined previously but Munc18c has just one that requires the N-peptide. These results indicate that the interactions between Munc18 and Syntaxin proteins, and the consequences for in vivo function, are more complex than can be accounted for by binding specificity alone. |
| Databáze: | OpenAIRE |
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