RGD Reference Report - Regenerating islet-derived 1alpha (Reg-1alpha) protein is new neuronal secreted factor that stimulates neurite outgrowth via exostosin Tumor-like 3 (EXTL3) receptor. - Rat Genome Database

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Regenerating islet-derived 1alpha (Reg-1alpha) protein is new neuronal secreted factor that stimulates neurite outgrowth via exostosin Tumor-like 3 (EXTL3) receptor.

Authors: Acquatella-Tran Van Ba, I  Marchal, S  Francois, F  Silhol, M  Lleres, C  Michel, B  Benyamin, Y  Verdier, JM  Trousse, F  Marcilhac, A 
Citation: Acquatella-Tran Van Ba I, etal., J Biol Chem. 2012 Feb 10;287(7):4726-39. doi: 10.1074/jbc.M111.260349. Epub 2011 Dec 9.
RGD ID: 9850120
Pubmed: PMID:22158612   (View Abstract at PubMed)
PMCID: PMC3281625   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M111.260349   (Journal Full-text)

Regenerating islet-derived 1alpha (Reg-1alpha)/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-1alpha is overexpressed during the very early stages of Alzheimer disease, and Reg-1alpha deposits were detected in the brain of patients with Alzheimer disease. However, the physiological function of Reg-1alpha in neural cells remains unknown. Here, we show that Reg-1alpha is expressed in neuronal cell lines (PC12 and Neuro-2a) and in rat primary hippocampal neurons (E17.5). Reg-1alpha is mainly localized around the nucleus and at the membrane of cell bodies and neurites. Transient overexpression of Reg-1alpha or addition of recombinant Reg-1alpha significantly increases the number of cells with longer neurites by stimulating neurite outgrowth. These effects are abolished upon down-regulation of Reg-1alpha by siRNA and following inhibition of secreted Reg-1alpha by antibodies. Moreover, Reg-1alpha 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-1alpha on neurite outgrowth, and Reg-1alpha is not effective when EXTL3 overexpression is down-regulated by shRNA. Our findings indicate that Reg-1alpha regulates neurite outgrowth and suggest that this effect is mediated by its receptor EXTL3.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of dendrite extension  IMP 9850120 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dendrite membrane  IDA 9850120 RGD 
growth cone  IDA 9850120 RGD 
neuronal cell body membrane  IDA 9850120 RGD 
perinuclear region of cytoplasm  IDA 9850120 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
identical protein binding  IPIReg1a (Rattus norvegicus)9850120homodimerization and homotetramerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Reg1a  (regenerating family member 1 alpha)


Additional Information