Worley Paul F, Zeng Weizhong, Huang Guojin, Kim Joo Young, Shin Dong Min, Kim Min Seuk, Yuan Joseph P, Kiselyov Kirill, Muallem Shmuel
The Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell Calcium. 2007 Oct-Nov;42(4-5):363-71. doi: 10.1016/j.ceca.2007.05.007. Epub 2007 Jul 5.
Homers are scaffolding proteins that bind Ca(2+) signaling proteins in cellular microdomains. The Homers participate in targeting and localization of Ca(2+) signaling proteins in signaling complexes. However, recent work showed that the Homers are not passive scaffolding proteins, but rather they regulate the activity of several proteins within the Ca(2+) signaling complex in an isoform-specific manner. Homer2 increases the GAP activity of RGS proteins and PLCbeta that accelerate the GTPase activity of Galpha subunits. Homer1 gates the activity of TRPC channels, controls the rates of their translocation and retrieval from the plasma membrane and mediates the conformational coupling between TRPC channels and IP(3)Rs. Homer1 stimulates the activity of the cardiac and neuronal L-type Ca(2+) channels Ca(v)1.2 and Ca(v)1.3. Homer1 also mediates the communication between the cardiac and smooth muscle ryanodine receptor RyR2 and Ca(v)1.2 to regulate E-C coupling. In many cases the Homers function as a buffer to reduce the intensity of Ca(2+) signaling and create a negative bias that can be reversed by the immediate early gene form of Homer1. Hence, the Homers should be viewed as the buffers of Ca(2+) signaling that ensure a high spatial and temporal fidelity of the Ca(2+) signaling and activation of downstream effects.
亲代谢受体（Homers）是一种支架蛋白，可在细胞微结构域中结合Ca(2+)信号蛋白。亲代谢受体参与Ca(2+)信号蛋白在信号复合物中的靶向和定位。然而，最近的研究表明，亲代谢受体并非被动的支架蛋白，而是以异构体特异性方式调节Ca(2+)信号复合物中几种蛋白的活性。亲代谢受体2增加了RGS蛋白和磷脂酶Cβ（PLCβ）的GAP活性，从而加速Gα亚基的GTP酶活性。亲代谢受体1控制瞬时受体电位阳离子通道C亚族（TRPC）通道的活性，控制其从质膜转运和回收的速率，并介导TRPC通道与1,4,5-三磷酸肌醇受体（IP(3)Rs）之间的构象偶联。亲代谢受体1刺激心脏和神经元L型Ca(2+)通道Ca(v)1.2和Ca(v)1.3的活性。亲代谢受体1还介导心脏和平滑肌兰尼碱受体2（RyR2）与Ca(v)1.2之间的通讯，以调节兴奋-收缩偶联。在许多情况下，亲代谢受体起到缓冲作用，以降低Ca(2+)信号的强度，并产生一种负偏差，这种偏差可被亲代谢受体1的即早基因形式逆转。因此，亲代谢受体应被视为Ca(2+)信号的缓冲器，可确保Ca(2+)信号具有高时空保真度并激活下游效应。
