Na/K-ATPase beta1-subunit associates with neuronal growth regulator 1 (NEGR1) to participate in intercellular interactions
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Neuronal growth regulator 1 (NEGR1) is a GPI-anchored membraneprotein that is involved in neural cell adhesion and communication. Multiple genome wide association studies havefound that NEGR1 is a generic risk factor for multiple humandiseases, including obesity, autism, and depression. Recently,we reported that Negr1−/− mice showed a highly increased fatmass and affective behavior. In the present study, we identifiedNa/K-ATPase, beta1-subunit (ATP1B1) as an NEGR1 bindingpartner by yeast two-hybrid screening. NEGR1 and ATP1B1were found to form a relatively stable complex in cells, at leastpartially co-localizing in membrane lipid rafts. We found thatNEGR1 binds with ATP1B1 at its C-terminus, away from thebinding site for the alpha subunit, and may contribute to intercellularinteractions. Collectively, we report ATP1B1 as a novelNEGR1-interacting protein, which may help deciphering molecularnetworks underlying NEGR1-associated human diseases.
Abstract
Neuronal growth regulator 1 (NEGR1) is a GPI-anchored membraneprotein that is involved in neural cell adhesion and communication. Multiple genome wide association studies havefound that NEGR1 is a generic risk factor for multiple humandiseases, including obesity, autism, and depression. Recently,we reported that Negr1−/− mice showed a highly increased fatmass and affective behavior. In the present study, we identifiedNa/K-ATPase, beta1-subunit (ATP1B1) as an NEGR1 bindingpartner by yeast two-hybrid screening. NEGR1 and ATP1B1were found to form a relatively stable complex in cells, at leastpartially co-localizing in membrane lipid rafts. We found thatNEGR1 binds with ATP1B1 at its C-terminus, away from thebinding site for the alpha subunit, and may contribute to intercellularinteractions. Collectively, we report ATP1B1 as a novelNEGR1-interacting protein, which may help deciphering molecularnetworks underlying NEGR1-associated human diseases.
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