Differential disruption of autoinhibition and defect in assembly of cytoskeleton during cell division decide the fate of human DIAPH1-related cytoskeletopathy

Diaphanous-related formins1 (DIA1) is a protein, encoded by DIAPH1 and it assembles the unbranched actin microfilament and microtubule cytoskeleton. As it functions in blood cell as well as hair cell in the cochlea, constitutive activation by the disruption of autoinhibitory interactions between the diaphanous inhibitory domain (DID) and diaphanous auto regulatory domain (DAD) caused by the mutants in the DAD, was reported to result in both hearing loss and blood cell abnormalities. Here, we report the first mutant in the DID of humans with only hearing loss and reveal that the differential cell biological phenotypes of DIA1 during cell division appear to be potential determinants of the clinical severity of DIAPH1-related cytoskeletopathy in humans. (By Dr. Bong Jik Kim, https://jmg.bmj.com/content/early/2019/08/31/jmedgenet-2019-106282 )

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