RESUMO
Neural stem cells (NSCs) and neural progenitors (NPs) in the mammalian neocortex give rise to the main cell types of the nervous system. The biological behavior of these NSCs and NPs is regulated by extracellular niche derived autocrine-paracrine signaling factors on a developmental timeline. Our previous reports [Plos One 2010;5:e15341; J Neurochem 2011;117:565-578] have shown that chondroitin sulfate proteoglycan and ApolipoproteinE are autocrine-paracrine survival factors for NSCs. NogoA, a myelin related protein, is expressed in the cortical ventricular zones where NSCs reside. However, the functional role of Nogo signaling proteins in NSC behavior is not completely understood. In this study, we show that NogoA receptors, NogoR1 and PirB, are expressed in the ventricular zone where NSCs reside between E10.5 and 14.5 but not at E15.5. Nogo ligands stimulate NSC survival and proliferation in a dosage-dependent manner in vitro. NogoR1 and PirB are low and high affinity Nogo receptors, respectively and are responsible for the effects of Nogo ligands on NSC behavior. Inhibition of autocrine-paracrine Nogo signaling blocks NSC survival and proliferation. In NSCs, NogoR1 functions through Rho whereas PirB uses Shp1/2 signaling pathways to control NSC behavior. Taken together, this work suggests that Nogo signaling is an important pathway for survival of NSCs.
Assuntos
Proteínas da Mielina/metabolismo , Células-Tronco Neurais/citologia , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos/metabolismo , Transdução de Sinais , Apolipoproteínas E/metabolismo , Comunicação Autócrina/efeitos dos fármacos , Contagem de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Tamanho Celular , Sobrevivência Celular/efeitos dos fármacos , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Embrião de Mamíferos/citologia , Feminino , Proteínas Ligadas por GPI/deficiência , Proteínas Ligadas por GPI/metabolismo , Células HEK293 , Humanos , Proteínas da Mielina/deficiência , Proteínas da Mielina/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Proteínas Nogo , Receptor Nogo 1 , Comunicação Parácrina/efeitos dos fármacos , Prosencéfalo/embriologia , Prosencéfalo/metabolismo , Receptores de Superfície Celular/deficiência , Receptores Imunológicos/deficiência , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares/citologia , Esferoides Celulares/metabolismoRESUMO
BpHi006A cDNA is 1943 bp in length, and contains one putative open reading frame that is 795 bp long. The expression of BpHi006A was induced by BPH feeding. BpHi006A protein contains a N-terminal domain and a C-terminal domain of glutathione S-transferase, and therefore, it belongs to the superfamily of glutathione S-transferase. BpHi006A protein exhibited 61% amino acid sequence identity to tetrachloro-p-hydroquinone reductive dehalogenase-related protein of Arabidopsis thaliana. Sequence analysis of these two proteins indicates that they belong to a new group of plant GSTs.
