Trudeau Matthew C, Zagotta William N
Department of Physiology and Biophysics, Howard Hughes Medical Institute, University of Washington Medical School, Seattle, WA 98195, USA.
Neuron. 2002 Apr 11;34(2):197-207. doi: 10.1016/s0896-6273(02)00647-5.
A mutation in a cyclic nucleotide-gated channel (CNGA1) is associated with retinitis pigmentosa (RP), a common, inherited eye disease. Expression of mutant (CNGA1-RP) homomeric channels in Xenopus oocytes revealed no measurable differences compared to wild-type CNGA1 homomers. As native retinal rod CNG channels comprise CNGA1 and CNGB1 subunits, we coexpressed CNGA1-RP and CNGB1. Surprisingly, this subunit combination did not produce detectable channels at the membrane surface. We show that the mechanism underlying this defect involves an intersubunit interaction between CNGA1 and CNGB1 that was not formed between CNGA1-RP and CNGB1 subunits. In the absence of this interaction, a short N-terminal region in CNGB1 prevented membrane expression. Thus, disruption of a regulatory interaction by mutation in CNGA1 exposed a region of CNGB1 that disrupted surface expression of heteromeric CNGA1-RP/CNGB1 channels, accounting for this instance of RP.
环核苷酸门控通道（CNGA1）中的一种突变与色素性视网膜炎（RP）相关，RP是一种常见的遗传性眼病。与野生型CNGA1同源体相比，非洲爪蟾卵母细胞中突变型（CNGA1-RP）同源通道的表达未显示出可测量的差异。由于天然视网膜视杆细胞CNG通道由CNGA1和CNGB1亚基组成，我们共表达了CNGA1-RP和CNGB1。令人惊讶的是，这种亚基组合在膜表面并未产生可检测到的通道。我们表明，这种缺陷背后的机制涉及CNGA1和CNGB1之间的亚基间相互作用，而CNGA1-RP和CNGB1亚基之间并未形成这种相互作用。在没有这种相互作用的情况下，CNGB1中一个短的N端区域阻止了膜表达。因此，CNGA1中的突变破坏调节相互作用，暴露了CNGB1中一个破坏异源CNGA1-RP/CNGB1通道表面表达的区域，这就解释了这种RP病例。
