Central regulation of photosensitive membrane turnover in the lateral eye of Limulus, II: octopamine acts via adenylate cyclase/cAMP-dependent protein kinase to prime the retina for transient rhabdom shedding.
Central regulation of photosensitive membrane turnover in the lateral eye of Limulus, II: octopamine acts via adenylate cyclase/cAMP-dependent protein kinase to prime the retina for transient rhabdom shedding.
复制标题
鲎 II 侧眼光敏膜周转的中枢调节：章鱼胺通过腺苷酸环化酶/cAMP 依赖性蛋白激酶发挥作用，为视网膜短暂的横纹肌脱落做好准备。
DOI：
10.1017/s0952523804215097
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发表时间：
2004
影响因子：
1.9
通讯作者：
Jinks,RobertN
中科院分区：
文献类型：
--
作者：
Runyon,ScottL;Washicosky,KevinJ;Brenneman,RandallJ;Kelly,JeremyR;Khadilkar,RashmiV;Heacock,KevinF;McCormick,ShaelanM;Williams,KellyE;Jinks,RobertN
为什么光感受器每天翻转一部分光感受膜尚不清楚;然而，如果不能正确地这样做，会导致脊椎动物和无脊椎动物的视网膜退化。关于调控光感受膜脱落和更新的分子机制知之甚少。鲎侧眼中的感光细胞在每天早晨的黎明时，以一种短暂的同步爆发的方式翻转它们的感光膜（横纹肌）。瞬时横纹肌脱落（TRS）是鲎横纹肌更新的第一阶段，由黎明触发，但需要中枢昼夜节律钟至少3-5小时的过夜启动（Chamberlain & Barlow，1984）。我们先前确定，时钟使用神经递质章鱼胺（OA）为侧眼准备TRS（Khadilkar等人，2002），并在此报道OA通过Gs-偶联的腺苷酸环化酶（AC）/环腺苷3′，5 ′-单磷酸（cAMP）/cAMP依赖性蛋白激酶（PKA）信号级联反应引发眼TRS。长期视网膜内注射（6-7 h，1.4 μl/min）AC激活剂毛喉素或cAMP类似物Sp-cAMP[S]和8-Br-cAMP，在与生物钟断开连接的眼睛和/或在生物钟静止的白天，在完整的眼睛中引发视网膜TRS。这表明OA通过刺激AC介导的细胞内cAMP浓度（[cAMP]i）升高来引发眼睛的TRS。与单独用OA治疗的眼睛相比，AC抑制剂SQ 22，536或PKA抑制剂H-89和PKI（14-22）与OA的共注射通过减少针对TRS致敏的光感受器的数量和由这些光感受器脱落的横纹的量来有效地拮抗章鱼胺能致敏。我们的数据表明，OA引发侧眼TRS部分通过长期磷酸化的PKA底物。
Why photoreceptors turn over a portion of their photoreceptive membrane daily is not clear; however, failure to do so properly leads to retinal degeneration in vertebrates and invertebrates. Little is known about the molecular mechanisms that regulate shedding and renewal of photoreceptive membrane. Photoreceptor cells in the lateral eye of the horseshoe crab Limulus turn over their photoreceptive membrane (rhabdom) in a brief, synchronous burst in response to dawn each morning. Transient rhabdom shedding (TRS), the first phase of rhabdom turnover in Limulus, is triggered by dawn, but requires a minimum of 3–5 h of overnight priming from the central circadian clock (Chamberlain & Barlow, 1984). We determined previously that the clock primes the lateral eye for TRS using the neurotransmitter octopamine (OA) (Khadilkar et al., 2002), and report here that OA primes the eye for TRS through a Gs-coupled, adenylate cyclase (AC)/cyclic adenosine 3′,5′-monophosphate (cAMP)/cAMP-dependent protein kinase (PKA) signaling cascade. Long-term intraretinal injections (6–7 h @ 1.4 μl/min) of the AC activator forskolin, or the cAMP analogs Sp-cAMP[S] and 8-Br-cAMP primed the retina for TRS in eyes disconnected from the circadian clock, and/or in intact eyes during the day when the clock is quiescent. This suggests that OA primes the eye for TRS by stimulating an AC-mediated rise in intracellular cAMP concentration ([cAMP]i). Co-injection of SQ 22,536, an AC inhibitor, or the PKA inhibitors H-89 and PKI (14-22) with OA effectively antagonized octopaminergic priming by reducing the number of photoreceptors primed for TRS and the amount of rhabdom shed by those photoreceptors compared with eyes treated with OA alone. Our data suggest that OA primes the lateral eye for TRS in part through long-term phosphorylation of a PKA substrate.