Wang Philip Y, Seabold Gail K, Wenthold Robert J
Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Mol Cell Neurosci. 2008 Sep;39(1):83-94. doi: 10.1016/j.mcn.2008.05.019. Epub 2008 Jun 7.
SALMs are a family of five adhesion molecules whose expression is largely restricted to the CNS. Initial reports showed that SALM1 functions in neurite outgrowth while SALM2 is involved in synapse formation. To investigate the function of SALMs in detail, we asked if all five are involved in neurite outgrowth. Expression of epitope-tagged proteins in cultured hippocampal neurons showed that SALMs are distributed throughout neurons, including axons, dendrites, and growth cones. Over-expression of each SALM resulted in enhanced neurite outgrowth, but with different phenotypes. Neurite outgrowth could be reduced by applying antibodies targeting the extracellular leucine rich regions of SALMs and with RNAi. Through over-expression of deletion constructs, we found that the C-terminal PDZ binding domains of SALMs 1-3 are required for most aspects of neurite outgrowth. In addition, by using a chimera of SALMs 2 and 4, we found that the N-terminus is also involved in neurite outgrowth.
SALM 是一个由五种黏附分子组成的家族,其表达主要局限于中枢神经系统。最初的报告显示,SALM1 在神经突生长中起作用,而 SALM2 参与突触形成。为了详细研究 SALM 的功能,我们询问这五种分子是否都参与神经突生长。在培养的海马神经元中表达表位标记蛋白表明,SALM 分布于整个神经元,包括轴突、树突和生长锥。每种 SALM 的过表达都导致神经突生长增强,但具有不同的表型。通过应用针对 SALM 细胞外富含亮氨酸区域的抗体和 RNA 干扰,可以减少神经突生长。通过缺失构建体的过表达,我们发现 SALM 1 - 3 的 C 末端 PDZ 结合结构域是神经突生长大多数方面所必需的。此外,通过使用 SALM 2 和 4 的嵌合体,我们发现 N 末端也参与神经突生长。