title: Regenerating islet-derived 1α (Reg-1α) protein is new neuronal secreted factor that stimulates neurite outgrowth via exostosin Tumor-like 3 (EXTL3) receptor.
abstract: Regenerating islet-derived 1α (Reg-1α)/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-1α is overexpressed during the very early stages of Alzheimer disease, and Reg-1α deposits were detected in the brain of patients with Alzheimer disease. However, the physiological function of Reg-1α in neural cells remains unknown. Here, we show that Reg-1α is expressed in neuronal cell lines (PC12 and Neuro-2a) and in rat primary hippocampal neurons (E17.5). Reg-1α is mainly localized around the nucleus and at the membrane of cell bodies and neurites. Transient overexpression of Reg-1α or addition of recombinant Reg-1α significantly increases the number of cells with longer neurites by stimulating neurite outgrowth. These effects are abolished upon down-regulation of Reg-1α by siRNA and following inhibition of secreted Reg-1α by antibodies. Moreover, Reg-1α 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-1α on neurite outgrowth, and Reg-1α is not effective when EXTL3 overexpression is down-regulated by shRNA. Our findings indicate that Reg-1α regulates neurite outgrowth and suggest that this effect is mediated by its receptor EXTL3.
authors.affiliation: University Montpellier 2, F-34095 Montpellier, France, INSERM, U710, F-34095 Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Acquatella-Tran Van Ba
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marchal
authors.forename: Florence
authors.initials: F
authors.lastname: François
authors.forename: Michèle
authors.initials: M
authors.lastname: Silhol
authors.forename: Coline
authors.initials: C
authors.lastname: Lleres
authors.forename: Bernard
authors.initials: B
authors.lastname: Michel
authors.forename: Yves
authors.initials: Y
authors.lastname: Benyamin
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Verdier
authors.forename: Françoise
authors.initials: F
authors.lastname: Trousse
authors.forename: Anne
authors.initials: A
authors.lastname: Marcilhac
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051847:Lithostathine / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: C110774:EXTL3 protein, human; C484685:Extl3 protein, mouse; D051847:Lithostathine; D009419:Nerve Tissue Proteins; C497617:REG1A protein, human; D011994:Recombinant Proteins; C497615:Reg1 protein, mouse; C497616:Reg1a protein, rat; D017351:N-Acetylglucosaminyltransferases