Molecular determinants of response kinetics of mouse M1 intrinsically-photosensitive retinal ganglion cells.
Molecular determinants of response kinetics of mouse M1 intrinsically-photosensitive retinal ganglion cells.
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DOI：
10.1038/s41598-021-02832-9
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发表时间：
2021-12-06
影响因子：
4.6
通讯作者：
Yau KW
中科院分区：
文献类型：
--
作者：
Sheng Y;Chen L;Ren X;Jiang Z;Yau KW
固有光敏视网膜神经节细胞（ipRGCs）是一种非杆状/非锥状视网膜光感受器，表达视觉色素黑视素，用于检测各种非图像形成视觉功能的环境辐照度。m1亚型是研究得最好的亚型之一，主要介导昼夜光干扰和瞳孔光反射。即使在单光子水平上，它们的固有光响应也比杆状和锥状细胞的光响应更长，这与非图像形成视觉的典型慢时间过程相一致。短（OPN4S）和长（OPN4L）交替剪接形式的黑视素蛋白都存在于m1 - iprgc中，但它们的功能差异尚不清楚。我们通过在小鼠中基因移除Opn4基因（Opn4−/−），并使用腺相关病毒在Opn4−/−小鼠中单独重新表达OPN4S或OPN4L来检验这一点，但发现它们内在的暗闪反应没有明显差异。先前的研究表明，M1-ipRGC光导的两个主要缓慢步骤决定了这些细胞固有的暗闪响应动力学，其时间常数（τ1和τ2）在室温下分别为~ 2 s和~ 20 s。在这里，我们发现通过磷酸化或β-阻滞蛋白使黑视素失活可能不是这两个步骤之一，因为它们的遗传破坏不会延长这两个时间常数或影响响应波形。在M1-ipRGC光导过程中，破坏效应酶PLCβ4上的GAP （gtpase - activation -protein）活性以减缓g蛋白的失活，也没有延长响应衰减，但通过产生第三个时间常数τ3（室温），使其上升阶段变得稍微s型。最后的观察结果表明，gap介导的g蛋白失活确实参与了闪光反应的终止，尽管通常时间常数太短，无法在响应波形中看到。
Intrinsically-photosensitive retinal ganglion cells (ipRGCs) are non-rod/non-cone retinal photoreceptors expressing the visual pigment, melanopsin, to detect ambient irradiance for various non-image-forming visual functions. The M1-subtype, amongst the best studied, mediates primarily circadian photoentrainment and pupillary light reflex. Their intrinsic light responses are more prolonged than those of rods and cones even at the single-photon level, in accordance with the typically slower time course of non-image-forming vision. The short (OPN4S) and long (OPN4L) alternatively-spliced forms of melanopsin proteins are both present in M1-ipRGCs, but their functional difference is unclear. We have examined this point by genetically removing the Opn4 gene (Opn4−/−) in mouse and re-expressing either OPN4S or OPN4L singly in Opn4−/− mice by using adeno-associated virus, but found no obvious difference in their intrinsic dim-flash responses. Previous studies have indicated that two dominant slow steps in M1-ipRGC phototransduction dictate these cells’ intrinsic dim-flash-response kinetics, with time constants (τ1 and τ2) at room temperature of ~ 2 s and ~ 20 s, respectively. Here we found that melanopsin inactivation by phosphorylation or by β-arrestins may not be one of these two steps, because their genetic disruptions did not prolong the two time constants or affect the response waveform. Disruption of GAP (GTPase-Activating-Protein) activity on the effector enzyme, PLCβ4, in M1-ipRGC phototransduction to slow down G-protein deactivation also did not prolong the response decay, but caused its rising phase to become slightly sigmoidal by giving rise to a third time constant, τ3, of ~ 2 s (room temperature). This last observation suggests that GAP-mediated G-protein deactivation does partake in the flash-response termination, although normally with a time constant too short to be visible in the response waveform.
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DOI：
10.1085/jgp.201311033
发表时间：
2014-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Itsuki K;Imai Y;Hase H;Okamura Y;Inoue R;Mori MX
通讯作者：
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影响因子：
2.9
作者：
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DOI：
10.1523/jneurosci.5391-09.2010
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The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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通讯作者：
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影响因子：
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