Deafness causing neuroplastin missense variants fail to promote plasma membrane Ca²⁺-ATPase levels and Ca²⁺ transient regulation in brain neurons.

ABSTRACT: Hearing, the ability to sense sounds, and the processing of auditory information are important for perception of the world. Mice lacking expression of neuroplastin (Np), a type-1 transmembrane glycoprotein, display deafness, multiple cognitive deficiencies, and reduced expression of plasma membrane calcium (Ca²⁺) ATPases (PMCAs) in cochlear hair cells and brain neurons. In this study, we transferred the deafness causing missense mutations pitch (C315S) and audio-1 (I122N) into human Np (hNp) constructs and investigated their effects at the molecular and cellular levels. Computational molecular dynamics show that loss of the disulfide bridge in hNp^pitch causes structural destabilization of immunoglobulin-like domain (Ig) III and that the novel asparagine in hNp^aud

SUBMITTER: Liang Y 

PROVIDER: S-EPMC11264175 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature