Gil Orlando D, Zhang Li, Chen Suzanne, Ren Y Q, Pimenta Aurea, Zanazzi George, Hillman Dean, Levitt Pat, Salzer James L
Department of Cell Biology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
J Neurobiol. 2002 Jun 5;51(3):190-204. doi: 10.1002/neu.10050.
Neurotrimin (Ntm) and the limbic system-associated membrane protein (LAMP) are members of the IgLON (LAMP, OBCAM, Ntm) family of glycorylphosphatidylinositol anchored neural cell adhesion molecules. We previously reported that LAMP and Ntm promote adhesion and neurite outgrowth via a homophilic mechanism, suggesting that these proteins promote the formation of specific neuronal circuits by homophilic interactions. In this report, we have further characterized the expression and binding specificity of Ntm. Using a newly generated monoclonal antibody to Ntm, we demonstrated that this protein is largely expressed in a complementary pattern to that of LAMP in the nervous system, with co-expression at a few sites. Ntm is expressed at high levels in sensory-motor cortex and, of particular note, is transiently expressed in neurons of cortical barrel fields and corresponding thalamic "barreloids." Binding of a recombinant, soluble form of Ntm to CHO cells expressing either Ntm or LAMP demonstrates that Ntm and LAMP interact both homophilically and heterophilically. In contrast to conventional growth-promoting activity of Ig superfamily members, LAMP strongly inhibits the outgrowth of Ntm-expressing dorsal root ganglion (DRG) neurons in a heterophilic manner. These anatomical and functional data support the concept that homophilic and heterophilic interactions between IgLON family members are likely to play a role in the specification of neuronal projections via growth promoting and inhibiting effects, respectively.
神经微蛋白（Ntm）和边缘系统相关膜蛋白（LAMP）是糖基磷脂酰肌醇锚定神经细胞粘附分子的IgLON（LAMP、OBCAM、Ntm）家族成员。我们之前报道过，LAMP和Ntm通过同种亲和机制促进粘附和神经突生长，这表明这些蛋白质通过同种亲和相互作用促进特定神经元回路的形成。在本报告中，我们进一步对Ntm的表达和结合特异性进行了表征。使用新生成的针对Ntm的单克隆抗体，我们证明该蛋白在神经系统中的表达模式与LAMP基本互补，仅在少数位点共表达。Ntm在感觉运动皮层中高水平表达，特别值得注意的是，它在皮质桶状区的神经元和相应的丘脑“桶状小体”中短暂表达。重组可溶性形式的Ntm与表达Ntm或LAMP的CHO细胞的结合表明，Ntm和LAMP既能同种亲和相互作用，也能异种亲和相互作用。与Ig超家族成员传统的促生长活性相反，LAMP以异种亲和方式强烈抑制表达Ntm的背根神经节（DRG）神经元的生长。这些解剖学和功能数据支持了这样一种观点，即IgLON家族成员之间的同种亲和与异种亲和相互作用可能分别通过促进和抑制生长的作用，在神经元投射的特异性形成中发挥作用。
