美国约翰•霍普金斯大学的Wang等研究发现,磷酸肌醇特异性磷脂酶C (PLC) 的同工酶在果蝇的光转录等的多个过程中发挥作用。在果蝇的感光细胞中,由NORPA编码的PLCβ对TRP通道的激活起到关键作用。Wang等描述的PLCβ调节器——STOPS,编码了一种SOCS盒型蛋白质。STOPS的基因突变会导致NORPA的浓度降低,以及光刺激消失后光感停止信号的缺失。
以往的研究认为NORPA有作为PLC激活蛋白和GTP酶激活蛋白的双重作用。Wang等认为,由于野生型NORPA的低水平表达导致的光感反映的缓慢停止现象,可以通过加入正常量的改造NORPA来抑制。这种改造后的NORPA有野生型GAP的活性,但没有PLC的活性。
STOPS是迄今发现的可以特异性调节PLCβ蛋白浓度的第一个蛋白质。这项研究同时也表明,在体内,PLCβ的衍生物没有激活TRP通道的作用,只有传递信号的作用。
相关研究论文发表在2008年1月10日的《神经元》(Neuron)上。(科学网 武彦文/编译)
(《神经元》(Neuron),Vol 57, 56-68, 10 January 2008,Tao Wang, Craig Montell)
生物谷推荐原始出处:
Neuron, Vol 57, 56-68, 10 January 2008
Article
The SOCS Box Protein STOPS Is Required for Phototransduction through Its Effects on Phospholipase C
Tao Wang,1,3 Xiaoyue Wang,1,3 Qiang Xie,2 and Craig Montell1,
1 Departments of Biological Chemistry and Neuroscience, Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2 School of Optometry, Indiana University, Bloomington, IN 47405, USA
Corresponding author
Craig Montell
cmontell@jhmi.edu
Summary
Phosphoinositide-specific phospholipase C (PLC) isozymes play roles in a diversity of processes including Drosophila phototransduction. In fly photoreceptor cells, the PLCβ encoded by norpA is critical for activation of TRP channels. Here, we describe a PLCβ regulator, STOPS, which encodes a SOCS box protein. Mutation of stops resulted in a reduced concentration of NORPA and a defect in stopping signaling following cessation of the light stimulus. NORPA has been proposed to have dual roles as a PLC- and GTPase-activating protein (GAP). We found that the slow termination resulting from expressing low levels of wild-type NORPA was suppressed by addition of normal amounts of an altered NORPA, which had wild-type GAP activity, but no PLC activity. STOPS is the first protein identified that specifically regulates PLCβ protein concentration. Moreover, this work demonstrates that a PLCβ derivative that does not promote TRP channel activation, still contributes to signaling in vivo.