来自基因技术公司肿瘤生物与血管新生研究部，Lexicon Pharmaceuticals公司的研究人员发现了Tspan12在视网膜血管生成过程中的重要作用。这一研究成果公布在Cell杂志上。
Wnt受体Frizzled-4 (FZD4)，共受体LRP5，或者配基Norrin的编码基因发生突变会扰乱视网膜血管的发育，引起眼科疾病（ophthalmic diseases），其中Norrin虽然与Wnts没有结构上的相关性，但是Norrin能与FZD4结合，从而激活Wnt途径。
在这篇文章中，研究人员发现了一种重要的视网膜血管蛋白：四旋蛋白Tspan12，这种蛋白在视网膜血管中表达，在FZD，LRP5，和Norrin突变小鼠中，可以发现Tspan12拟表型缺失。而且Tspan12也与LRP5，和Norrin存在遗传相关性。
进一步研究发现，Tspan12的过量表达能通过作用于Norrin受体复合物，极大增加Norrin/β-catenin的表达，而不是如之前发现的，促进Wnt/β-catenin的表达，并且Tspan12 siRNA能抑制的是Norrin的转录应答，而不是Wnt3A。
这些研究成果说明TAPAN12的重要作用，与Norrin多聚物互作，促进FZD4多聚物的形成，以及提升相关信号途径的生理水平。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell, Volume 139,16 October 2009 doi:10.1016/j.cell.2009.07.048
TSPAN12 Regulates Retinal Vascular Development by Promoting Norrin- but Not Wnt-Induced FZD4/β-Catenin Signaling
Harald J. Junge1, Stacey Yang1, 5, Jeremy B. Burton1, 5, Kim Paes4, Xiao Shu1, 6, Dorothy M. French2, Mike Costa3, Dennis S. Rice4 and Weilan Ye1, ,
1 Tumor Biology and Angiogenesis Department, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA
2 Pathology Department, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA
3 Department of Cancer Targets, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA
4 Ophthalmology Department, Lexicon Pharmaceuticals Inc., 8800 Technology Forest, The Woodlands, TX 77381-1160, USA
Mutations in the genes encoding the Wnt receptor Frizzled-4 (FZD4), coreceptor LRP5, or the ligand Norrin disrupt retinal vascular development and cause ophthalmic diseases. Although Norrin is structurally unrelated to Wnts, it binds FZD4 and activates the canonical Wnt pathway. Here we show that the tetraspanin Tspan12 is expressed in the retinal vasculature, and loss of Tspan12 phenocopies defects seen in Fzd4, Lrp5, and Norrin mutant mice. In addition, Tspan12 genetically interacts with Norrin or Lrp5. Overexpressed TSPAN12 associates with the Norrin-receptor complex and significantly increases Norrin/β-catenin but not Wnt/β-catenin signaling, whereas Tspan12 siRNA abolishes transcriptional responses to Norrin but not Wnt3A in retinal endothelial cells. Signaling defects caused by Norrin or FZD4 mutations that are predicted to impair receptor multimerization are rescued by overexpression of TSPAN12. Our data indicate that Norrin multimers and TSPAN12 cooperatively promote multimerization of FZD4 and its associated proteins to elicit physiological levels of signaling.
