a potential role for shed soluble major histocompatibility class i molecules as modulators of neurite outgrowth摆脱可溶性的潜在作用主要组织相容性一级分子神经突结果的调节器.pdfVIP

A Potential Role for Shed Soluble Major Histocompatibility Class I Molecules as Modulators of Neurite Outgrowth 1. 1. 2 1 1 1 Lorraine R. Washburn , Dan Zekzer , Shoshana Eitan , Yuxin Lu , Hoa Dang , Blake Middleton , 2 1 1 Christopher J. Evans , Jide Tian , Daniel L. Kaufman * 1 Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California, United States of America, 2 Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, United States of America Abstract The neurobiological activities of classical major histocompatibility class I (MHCI) molecules are just beginning to be explored. To further examine MHCI’s actions during the formation of neuronal connections, we cultured embryonic mouse retina explants a short distance from wildtype thalamic explants, or thalami from transgenic mice (termed ‘‘NSE-Db’’) whose neurons express higher levels of MHCI. While retina neurites extended to form connections with wildtype thalami, we were surprised to find that retina neurite outgrowth was very stunted in regions proximal to NSE-Db thalamic explants, suggesting that a diffusible factor from these thalami inhibited retina neurite outgrowth. It has been long known that MHCI- expressing cells release soluble forms of MHCI (sMHCI) due to the shedding of intact MHCI molecules, as well as the alternative exon splicing of its heavy chain or the action proteases which cleave off it’s transmembrane anchor. We show that the diffusible inhibitory factor from the NSE-Db thalami is sM