We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation.
- Authors
Petrushanko, Irina Yu.; Tverskoi, Artem M.; Barykin, Evgeny P.; Petrovskaya, Aleksandra V.; Strelkova, Maria A.; Leonova, Olga G.; Anashkina, Anastasia A.; Tolstova, Anna P.; Adzhubei, Alexei A.; Bogdanova, Anna Yu.; Makarov, Alexander A.; Mitkevich, Vladimir A.
- Abstract
Beta-amyloid (Aβ) has a dual role, both as an important factor in the pathology of Alzheimer's disease and as a regulator in brain physiology. The inhibitory effect of Aβ42 oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer's disease. Still, the physiological role of the monomeric form of Aβ42 interaction with Na,K-ATPase remains unclear. We report that Na,K-ATPase serves as a receptor for Aβ42 monomer, triggering Src kinase activation. The co-localization of Aβ42 with α1- and β1-subunits of Na,K-ATPase, and Na,K-ATPase with Src kinase in SH-SY5Y neuroblastoma cells, was observed. Treatment of cells with 100 nM Aβ42 causes Src kinase activation, but does not alter Na,K-ATPase transport activity. The interaction of Aβ42 with α1β1 Na,K-ATPase isozyme leads to activation of Src kinase associated with the enzyme. Notably, prevention of Na,K-ATPase:Src kinase interaction by a specific inhibitor pNaKtide disrupts the Aβ-induced Src kinase activation. Stimulatory effect of Aβ42 on Src kinase was lost under hypoxic conditions, which was similar to the effect of specific Na,K-ATPase ligands, the cardiotonic steroids. Our findings identify Na,K-ATPase as a Aβ42 receptor, thus opening a prospect on exploring the physiological and pathological Src kinase activation caused by Aβ42 in the nervous system.
- Subjects
BIBLE. Acts; ALZHEIMER'S disease; CARDIAC glycosides; BRAIN physiology; NERVOUS system; MONOMERS; PROTEIN kinase C
- Publication
Cells (2073-4409), 2022, Vol 11, Issue 17, p2753
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells11172753