Vielmetter J, Kayyem J F, Roman J M, Dreyer W J
Division of Biology, California Institute of Technology, Pasadena 91125.
J Cell Biol. 1994 Dec;127(6 Pt 2):2009-20. doi: 10.1083/jcb.127.6.2009.
Using a monoclonal antibody, we have identified and characterized a previously unknown cell surface protein in chicken that we call neogenin and have determined its primary sequence. The deduced amino acid sequence and structure of neogenin characterize it as a member of the immunoglobulin (Ig) superfamily. Based on amino acid sequence similarities, neogenin is closely related to the human tumor suppressor molecule DCC (deleted in colorectal cancer). Neogenin and DCC define a subgroup of Ig superfamily proteins structurally distinct from other Ig molecules such as N-CAM, Ng-CAM, and Bravo/Nr-CAM. As revealed by antibody staining of tissue sections and Western blots, neogenin expression correlates with the onset of neuronal differentiation. Neogenin is also found on cells in the lower gastrointestinal tract of embryonic chickens. DCC has been observed in human neural tissues and has been shown to be essential for terminal differentiation of specific cell types in the adult human colon. These parallels suggest that neogenin, like DCC, is functionally involved in the transition from cell proliferation to terminal differentiation of specific cell types. Since neogenin is expressed on growing neurites and downregulated at termination of neurite growth, it may also play an important role in many of the complex functional aspects of neurite extension and intercellular signaling.
利用单克隆抗体,我们在鸡中鉴定并表征了一种以前未知的细胞表面蛋白,我们将其命名为新生蛋白,并确定了其一级序列。新生蛋白推导的氨基酸序列和结构表明它是免疫球蛋白(Ig)超家族的成员。基于氨基酸序列的相似性,新生蛋白与人类肿瘤抑制分子DCC(在结直肠癌中缺失)密切相关。新生蛋白和DCC定义了Ig超家族蛋白的一个亚组,其结构与其他Ig分子如N-CAM、Ng-CAM和Bravo/Nr-CAM不同。组织切片的抗体染色和蛋白质印迹显示,新生蛋白的表达与神经元分化的开始相关。在胚胎鸡的下消化道细胞中也发现了新生蛋白。DCC已在人类神经组织中观察到,并已证明对成人结肠中特定细胞类型的终末分化至关重要。这些相似之处表明,新生蛋白与DCC一样,在特定细胞类型从细胞增殖向终末分化的转变中发挥功能作用。由于新生蛋白在生长的神经突上表达,并在神经突生长终止时下调,它可能在神经突延伸和细胞间信号传导的许多复杂功能方面也发挥重要作用。