Molecular basis of human Usher syndrome: Deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher disease

Basement Membranes: Cell Scaffoldings and Signaling Platforms

“…The shorter (a) version consists of a tandem array of laminin LG, laminin LN, ten LE repeats, and four fibronectin type 3 repeats. The longer version contains additional fibronectin repeats with distal transmembrane and cytoplasmic domains (reviewed in Reiners et al 2006). Its absence is a cause of Usher syndrome type 2A characterized by hearing impairment and retinitis pigmentosa.…”

Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells

“…There have been conflicting reports about usherin tissue distribution and subcellular localization (4,13,(16)(17)(18). The putative 600-kDa full-length protein never was confirmed from native tissues, and the function of usherin was poorly understood.…”

Clarin-1 acts as a modulator of mechanotransduction activity and presynaptic ribbon assembly

“…Mutations in their corresponding genes are associated with Usher syndrome type I and nonsyndromic hearing loss (Bolz et al, 2001;Ahmed et al, 2003Ahmed et al, , 2006Schultz et al, 2011). Several interactions between these and other Usher proteins have been described (Reiners et al, 2006;Zallocchi et al, 2010Zallocchi et al, , 2012aCaberlotto et al, 2011). Because the absence of clarin-1 results in dysfunction of the mechanotransduction machinery, we addressed whether clarin-1, Pcdh15a, and/or Cdh23 were part of a protein complex in fish the hair cell bundles and that perturbations in clarin-1/Pcdh15a interactions lead, at least in part, to mechanotransduction channel dysfunction.…”