Regenerating islet-derived 1? (Reg-1?) protein is new neuronal secreted factor that stimulates neurite outgrowth via exostosin Tumor-like 3 (EXTL3) receptor.
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ABSTRACT: Regenerating islet-derived 1? (Reg-1?)/lithostathine, a member of a family of secreted proteins containing a C-type lectin domain, is expressed in various organs and plays a role in proliferation, differentiation, inflammation, and carcinogenesis of cells of the digestive system. We previously reported that Reg-1? is overexpressed during the very early stages of Alzheimer disease, and Reg-1? deposits were detected in the brain of patients with Alzheimer disease. However, the physiological function of Reg-1? in neural cells remains unknown. Here, we show that Reg-1? is expressed in neuronal cell lines (PC12 and Neuro-2a) and in rat primary hippocampal neurons (E17.5). Reg-1? is mainly localized around the nucleus and at the membrane of cell bodies and neurites. Transient overexpression of Reg-1? or addition of recombinant Reg-1? significantly increases the number of cells with longer neurites by stimulating neurite outgrowth. These effects are abolished upon down-regulation of Reg-1? by siRNA and following inhibition of secreted Reg-1? by antibodies. Moreover, Reg-1? colocalizes with exostosin tumor-like 3 (EXTL3), its putative receptor, at the membrane of these cells. Overexpression of EXTL3 increases the effect of recombinant Reg-1? on neurite outgrowth, and Reg-1? is not effective when EXTL3 overexpression is down-regulated by shRNA. Our findings indicate that Reg-1? regulates neurite outgrowth and suggest that this effect is mediated by its receptor EXTL3.
SUBMITTER: Acquatella-Tran Van Ba I
PROVIDER: S-EPMC3281625 | biostudies-literature | 2012 Feb
REPOSITORIES: biostudies-literature
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