Osten Pavel, Stern-Bach Yael
Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL 60611, USA.
Curr Opin Neurobiol. 2006 Jun;16(3):275-80. doi: 10.1016/j.conb.2006.04.002. Epub 2006 May 5.
The stargazin gene (also referred to as Cacng2) has been identified by forward genetics in a spontaneous mouse mutant with ataxic gait, upward head-elevating movements (hence the name stargazer for the mouse) and episodes of spike-wave discharges. Stargazin is related to the gamma-1 subunit of skeletal muscle voltage-dependent calcium channel (VDCC), and a deficit in its role as auxiliary VDCC subunit was proposed to underlie the epileptic phenotype of the mouse; yet, a conclusive demonstration of stargazin function in VDCC regulation is still lacking. In contrast, stargazin and its three closely related isoforms gamma-3, gamma-4 and gamma-8 were shown to function as auxiliary subunits for a very different ion channel - the AMPA-type glutamate receptor - prominently regulating early intracellular transport, synaptic targeting and anchoring, and ion channel functions of this major excitatory receptor in the brain.
在一个表现出共济失调步态、头部向上抬起运动（因此该小鼠被命名为凝视者）以及棘波放电发作的自发小鼠突变体中，通过正向遗传学鉴定出了凝视蛋白基因（也称为Cacng2）。凝视蛋白与骨骼肌电压依赖性钙通道（VDCC）的γ-1亚基相关，其作为辅助VDCC亚基的功能缺陷被认为是该小鼠癫痫表型的基础；然而，仍缺乏关于凝视蛋白在VDCC调节中功能的确凿证据。相比之下，凝视蛋白及其三个密切相关的异构体γ-3、γ-4和γ-8被证明可作为一种非常不同的离子通道——AMPA型谷氨酸受体的辅助亚基，显著调节这种大脑中主要兴奋性受体的早期细胞内运输、突触靶向和锚定以及离子通道功能。
