nArgBP2 regulates excitatory synapse formation by controlling dendritic spine morphology
| العنوان: | nArgBP2 regulates excitatory synapse formation by controlling dendritic spine morphology |
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| المؤلفون: | Sunghoe Chang, Hoyong Park, Yoonju Kim, Unghwi Lee, Myeongsu Na, Sangeun Lee, Jeong Kyu Han, Soomin Jeong, Gianluca Cestra, ChiHye Chung |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America 113 (2016): 6749–6754. doi:10.1073/pnas.1600944113 info:cnr-pdr/source/autori:Lee, Sang-Eun; Kim, Yoonju; Han, Jeong-Kyu; Park, Hoyong; Lee, Unghwi; Na, Myeongsu; Jeong, Soomin; Chung, ChiHye; Cestra, Gianluca; Chang, Sunghoe/titolo:nArgBP2 regulates excitatory synapse formation by controlling dendritic spine morphology/doi:10.1073%2Fpnas.1600944113/rivista:Proceedings of the National Academy of Sciences of the United States of America/anno:2016/pagina_da:6749/pagina_a:6754/intervallo_pagine:6749–6754/volume:113 |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Dendritic spine, Bipolar Disorder, Dendritic Spines, excitatory synapse, macromolecular substances, Biology, Synapse, Rats, Sprague-Dawley, 03 medical and health sciences, Mice, 0302 clinical medicine, Excitatory synapse, nArgBP2, Postsynaptic potential, mental disorders, Animals, Protein Isoforms, Adaptor Proteins, Signal Transducing, Multidisciplinary, Cofilin, Biological Sciences, Actin cytoskeleton, Cell biology, Rats, 030104 developmental biology, Gene Knockdown Techniques, Synapses, Excitatory postsynaptic potential, actin, Postsynaptic density, 030217 neurology & neurosurgery |
| الوصف: | Neural Abelson-related gene-binding protein 2 (nArgBP2) was originally identified as a protein that directly interacts with synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3), a postsynaptic scaffolding protein critical for the assembly of glutamatergic synapses. Although genetic deletion of nArgBP2 in mice leads to manic/bipolar-like behaviors resembling many aspects of symptoms in patients with bipolar disorder, the actual function of nArgBP2 at the synapse is completely unknown. Here, we found that the knockdown (KD) of nArgBP2 by specific small hairpin RNAs (shRNAs) resulted in a dramatic change in dendritic spine morphology. Reintroducing shRNA-resistant nArgBP2 reversed these defects. In particular, nArgBP2 KD impaired spine-synapse formation such that excitatory synapses terminated mostly at dendritic shafts instead of spine heads in spiny neurons, although inhibitory synapse formation was not affected. nArgBP2 KD further caused a marked increase of actin cytoskeleton dynamics in spines, which was associated with increased Wiskott-Aldrich syndrome protein-family verprolin homologous protein 1 (WAVE1)/p21-activated kinase (PAK) phosphorylation and reduced activity of cofilin. These effects of nArgBP2 KD in spines were rescued by inhibiting PAK or activating cofilin combined with sequestration of WAVE. Together, our results suggest that nArgBP2 functions to regulate spine morphogenesis and subsequent spine-synapse formation at glutamatergic synapses. They also raise the possibility that the aberrant regulation of synaptic actin filaments caused by reduced nArgBP2 expression may contribute to the manifestation of the synaptic dysfunction observed in manic/bipolar disorder. |
| تدمد: | 1091-6490 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e8e32a077232fe5e39efceffdf8a95b https://pubmed.ncbi.nlm.nih.gov/27226294 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3e8e32a077232fe5e39efceffdf8a95b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 |
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