https://scholars.lib.ntu.edu.tw/handle/123456789/412515
標題: | Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation | 作者: | Hsiao, Yu Tien Shu, Wen Chi Chen, Pin Chun Yang, Hui Ju Chen, Hsin Yo Hsu, Sheng Ping Huang, Yi Ting Yang, Cheng Chang Chen, Yen Ju Yu, Ni Yen Liou, Shih Yuan Chiang, Ning Huang, Chien Ting Cheng, Tzu Lin Cheung, Lam Yan Lin, Yu Chun Lu, Juu Chin CHIH-TIEN WANG |
關鍵字: | PKA-mediated phosphorylation | Retinal waves | Retinogeniculate projection | SNAP-25 | Starburst amacrine cells | 公開日期: | 19-二月-2019 | 出版社: | NATL ACAD SCIENCES | 卷: | 116 | 期: | 8 | 起(迄)頁: | 3262-3267 | 來源出版物: | Proceedings of the National Academy of Sciences of the United States of America | 摘要: | © 2019 National Academy of Sciences. All Rights Reserved. Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/412515 | ISSN: | 00278424 | DOI: | https://api.elsevier.com/content/abstract/scopus_id/85061859419 10.1073/pnas.1812169116 |
顯示於: | 分子與細胞生物學研究所 |
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