Protein phosphatase‐1M and Rho‐kinase affect exocytosis from cortical synaptosomes and influence neurotransmission at a glutamatergic giant synapse of the rat auditory system
Protein phosphatase‐1M and Rho‐kinase affect exocytosis from cortical synaptosomes and influence neurotransmission at a glutamatergic giant synapse of the rat auditory system
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蛋白磷酸酶-1M和Rho激酶影响皮质突触体的胞吐作用并影响大鼠听觉系统谷氨酸能巨突触的神经传递
作者：
Beáta Lontay;B. Pál;Z. Serfőző;Á. Kőszeghy;G. Szücs;Z. Rusznák;F. Erdődi
蛋白磷酸酶‐1M （PP1M，肌球蛋白磷酸酶）由PP1催化亚基（PP1c）和肌球蛋白磷酸酶靶亚基‐1 （MYPT1）组成。RhoA活化激酶（ROK）通过抑制MYPT1的磷酸化来调节PP1M。采用多学科方法，我们研究了PP1M和ROK在神经传递中的作用。电镜显示MYPT1和ROK存在于突触前和突触后末端。TMC是一种PP1特异性抑制剂，可减少皮质突触体去极化诱导的胞外分泌。反式- 4‐[（1R）‐1‐氨基乙基]‐N‐4‐吡啶基环己anecarboxamide二盐酸盐是一种ROK特异性抑制剂，具有相反的效果。质谱分析鉴定出几种与MYPT1结合的突触体蛋白，其中突触素- 1、syntaxin - 1、钙调磷酸酶- A亚基和Ca2+/钙调蛋白依赖性激酶II与MYPT1相互作用。在完整的突触体中，TMC增加，而Y27632降低了MYPT1Thr696、myosin - II轻链ser19、synapsin - ISer9和syntaxin - 1Ser14的磷酸化水平，表明PP1M和ROK影响了它们的磷酸化状态。共聚焦显微镜显示，MYPT1和ROK在大鼠耳蜗腹侧核突触前和突触后均存在。听觉谷氨酸巨突触的神经传递分析表明，PP1M和ROK通过突触前和突触后机制影响神经传递。我们的数据表明PP1M和ROK都影响突触传递，但需要进一步的研究来充分说明它们的作用机制。
Protein phosphatase‐1M (PP1M, myosin phosphatase) consists of a PP1 catalytic subunit (PP1c) and the myosin phosphatase target subunit‐1 (MYPT1). RhoA‐activated kinase (ROK) regulates PP1M via inhibitory phosphorylation of MYPT1. Using multidisciplinary approaches, we have studied the roles of PP1M and ROK in neurotransmission. Electron microscopy demonstrated the presence of MYPT1 and ROK in both pre‐ and post‐synaptic terminals. Tautomycetin (TMC), a PP1‐specific inhibitor, decreased the depolarization‐induced exocytosis from cortical synaptosomes. trans‐4‐[(1R)‐1‐aminoethyl]‐N‐4‐pyridinylcyclohexanecarboxamide dihydrochloride, a ROK‐specific inhibitor, had the opposite effect. Mass spectrometry analysis identified several MYPT1‐bound synaptosomal proteins, of which interactions of synapsin‐I, syntaxin‐1, calcineurin‐A subunit, and Ca2+/calmodulin‐dependent kinase II with MYPT1 were confirmed. In intact synaptosomes, TMC increased, whereas Y27632 decreased the phosphorylation levels of MYPT1Thr696, myosin‐II light chainSer19, synapsin‐ISer9, and syntaxin‐1Ser14, indicating that PP1M and ROK influence their phosphorylation status. Confocal microscopy indicated that MYPT1 and ROK are present in the rat ventral cochlear nucleus both pre‐ and post‐synaptically. Analysis of the neurotransmission in an auditory glutamatergic giant synapse demonstrated that PP1M and ROK affect neurotransmission via both pre‐ and post‐synaptic mechanisms. Our data suggest that both PP1M and ROK influence synaptic transmission, but further studies are needed to give a full account of their mechanism of action.
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DOI：
10.1046/j.1432-1327.2000.01158.x
发表时间：
2000-03-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Tóth, A;Kiss, E;Erdödi, F
通讯作者：
Erdödi, F
影响因子：
3.4
作者：
Moring,J;Shoemaker,WJ;Skita,V;Mason,RP;Hayden,HC;Salomon,RM;Herbette,LG
通讯作者：
Herbette,LG
DOI：
10.1016/j.ecolind.2023.110170
发表时间：
--
期刊：
Ecological Indicators
影响因子：
7.42
作者：
S. Köthe; N. Bakanov; C.A. Brühl; B. Gemeinholzer; T. Hörren; R. Mühlethaler; M. Sorg; H. Sumser; S.J. Swenson; G.U.C. Lehmann
通讯作者：
S. Köthe
影响因子：
3.1
作者：
Birukova, AA;Smurova, K;Verin, AD
通讯作者：
Verin, AD
影响因子：
4
作者：
P. Cohen
通讯作者：
P. Cohen