| First Author | Tavasoli M | Year | 2024 |
| Journal | Life Sci Alliance | Volume | 7 |
| Issue | 8 | PubMed ID | 38749543 |
| Mgi Jnum | J:348391 | Mgi Id | MGI:7640819 |
| Doi | 10.26508/lsa.202301956 | Citation | Tavasoli M, et al. (2024) Defects in integrin complex formation promote CHKB-mediated muscular dystrophy. Life Sci Alliance 7(8) |
| abstractText | Phosphatidylcholine (PC) is the major membrane phospholipid in most eukaryotic cells. Bi-allelic loss of function variants in CHKB, encoding the first step in the synthesis of PC, is the cause of a rostrocaudal muscular dystrophy in both humans and mice. Loss of sarcolemma integrity is a hallmark of muscular dystrophies; however, how this occurs in the absence of choline kinase function is not known. We determine that in Chkb (-/-) mice there is a failure of the alpha7beta1 integrin complex that is specific to affected muscle. We observed that in Chkb (-/-) hindlimb muscles there is a decrease in sarcolemma association/abundance of the PI(4,5)P(2) binding integrin complex proteins vinculin, and alpha-actinin, and a decrease in actin association with the sarcolemma. In cells, pharmacological inhibition of choline kinase activity results in internalization of a fluorescent PI(4,5)P(2) reporter from discrete plasma membrane clusters at the cell surface membrane to cytosol, this corresponds with a decreased vinculin localization at plasma membrane focal adhesions that was rescued by overexpression of CHKB. |
