Cotrafficking of SV2 and Synaptotagmin at the Synapse
| العنوان: | Cotrafficking of SV2 and Synaptotagmin at the Synapse |
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| المؤلفون: | Patricia Kensel-Hammes, Sandra M. Bajjalieh, Richard G. Gardner, Jia Yao, Amy Nowack |
| المصدر: | The Journal of Neuroscience. 30:5569-5578 |
| بيانات النشر: | Society for Neuroscience, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Mice, Knockout, Membrane Glycoproteins, Vesicle fusion, STX1A, General Neuroscience, Vesicle, Nerve Tissue Proteins, Biology, Synaptic vesicle, Endocytosis, Article, Synaptotagmin 1, Rats, Transport protein, Cell biology, Mice, Protein Transport, Synaptotagmins, Membrane protein, Synapses, Animals, Tyrosine, Clathrin adaptor proteins, Cells, Cultured, Protein Binding |
| الوصف: | Synaptic vesicles are specialized cycling endosomes that contain a unique constellation of membrane proteins. Proteins are sorted to vesicles by short amino acid sequences that serve as binding sites for clathrin adaptor proteins. Here we show that a tyrosine-based endocytosis motif in the vesicle protein SV2 is required for trafficking to synaptic vesicles of both SV2 and the calcium sensor protein synaptotagmin. Aberrant neurotransmission in cultured hippocampal neurons lacking SV2 was rescued by expression of wild-type SV2A, but not by SV2A-Y46A, a mutant containing a disrupted endocytosis motif in SV2A's cytoplasmic N terminus. Neurons expressing SV2A-Y46A had significantly more SV2 on the plasma membrane, indicating reduced internalization. A screen for proteins that preferentially bound wild-type SV2A identified multiple endocytosis-related proteins, andin vitrobinding studies confirmed binding to the clathrin adaptors AP2, EPS15, and amphiphysin 2/Bin1. Neurons lacking SV2 contained less synaptotagmin and had a higher proportion of synaptotagmin on the plasma membrane. Expression of either wild-type SV2A or SV2A-Y46A restored synaptotagmin expression levels; however, only wild-type SV2A restored a normal proportion of synaptotagmin on the plasma membrane. These findings indicate that SV2 influences the expression and trafficking of synaptotagmin via separate mechanisms. Synaptic vesicles immunoisolated from SV2A/B double knock-out mice had significantly less synaptotagmin than vesicles isolated from wild-type mice. Our results indicate that SV2 plays a major role in regulating the amount of synaptotagmin in synaptic vesicles and provide an explanation for the observation that synapses lacking SV2 have fewer vesicles competent for calcium-induced fusion. |
| تدمد: | 1529-2401 0270-6474 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f0d504edf519cc820f8af5afea2da2d1 https://doi.org/10.1523/jneurosci.4781-09.2010 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f0d504edf519cc820f8af5afea2da2d1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292401 02706474 |
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