| First Author | Chen PJ | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 31 | Pages | 10677-10688 |
| PubMed ID | 32532815 | Mgi Jnum | J:300666 |
| Mgi Id | MGI:6472422 | Doi | 10.1074/jbc.RA120.013952 |
| Citation | Chen PJ, et al. (2020) Phosphorylation of alpha-dystrobrevin is essential for alphakap accumulation and acetylcholine receptor stability. J Biol Chem 295(31):10677-10688 |
| abstractText | The maintenance of a high density of the acetylcholine receptor (AChR) is the hallmark of the neuromuscular junction. Muscle-specific anchoring protein (alphakap) encoded within the calcium/calmodulin-dependent protein kinase IIalpha (CAMK2A) gene is essential for the maintenance of AChR clusters both in vivo and in cultured muscle cells. The underlying mechanism by which alphakap is maintained and regulated remains unknown. Here, using human cell lines, fluorescence microscopy, and pulldown and immunoblotting assays, we show that alpha-dystrobrevin (alpha-dbn), an intracellular component of the dystrophin glycoprotein complex, directly and robustly promotes the stability of alphakap in a concentration-dependent manner. Mechanistically, we found that the phosphorylatable tyrosine residues of alpha-dbn are essential for the stability of alpha-dbn itself and its interaction with alphakap, with substitution of three tyrosine residues in the alpha-dbn C terminus with phenylalanine compromising the alphakap-alpha-dbn interaction and significantly reducing both alphakap and alpha-dbn accumulation. Moreover, the alphakap-alpha-dbn interaction was critical for alphakap accumulation and stability. We also found that the absence of either alphakap or alpha-dbn markedly reduces AChRalpha accumulation and that overexpression of alpha-dbn or alphakap in cultured muscle cells promotes the formation of large agrin-induced AChR clusters. Collectively, these results indicate that the stability of alphakap and alpha-dbn complex plays an important role in the maintenance of high-level expression of AChRs. |
