Rab11a Is Essential for the Development and Integrity of the Stereocilia and Kinocilia in the Mammalian Organ of Corti

• Type of Material: Article
• Authors: Lindsey Knapp, Emory University; Haojie Sun, Fudan University; Yan-Mei Wang, Fudan University; Bin-Jun Chen, Eye and ENT Hospital of Fudan University; Xi Lin, Emory University; Nan Gao, Rutgers State University; Ping Chen, Emory University; Dongdong Ren, Emory University
• Language: English
• Date: 2023-06-01
• Publisher: SOC NEUROSCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Knapp et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/ENEURO.0420-22.2023
• Title of Journal or Parent Work: ENEURO
• Volume: 10
• Issue: 6
• Grant/Funding Information: This work was supported by the National Institutes of Health (NIH) Grant R01DK102934 (to N.G.), National Natural Science Foundation of China (NSFC) Grants 82271166, 81970880, and 81771017 (to D.R.), the Natural Science Foundation of Shanghai Grant No. 22ZR1410100 (to D.R.), and Emory University (L.K. and P.C.).
• Keywords: primary cilia; planar cell polarity; apical-basal protein targeting; MYOSIN VB; tip link; PROTEINS; VANGL2; NEURAL-TUBE CLOSURE; intraflagellar transport; Science & Technology; Neurosciences; Neurosciences & Neurology; MISSENSE MUTATION; PLANAR CELL POLARITY; TRANSDUCER ADAPTATION; HAIR-CELLS; TRANSPORT; stereocilia; INNER-EAR; Life Sciences & Biomedicine
• Research Categories: Biology, Cell; Health Sciences, Medicine and Surgery

Abstract

The cochlea hair cells transform mechanic sounds to neural signals with a remarkable sensitivity and resolution. This is achieved via the precisely sculpted mechanotransduction apparatus of the hair cells and the supporting structure of the cochlea. The shaping of the mechanotransduction apparatus, the staircased stereocilia bundles on the apical surface of the hair cells, requires an intricate regulatory network including planar cell polarity (PCP) and primary cilia genes in orienting stereocilia bundles and building molecular machinery of the apical protrusions. The mechanism linking these regulatory components is unknown. Here, we show that a small GTPase known for its role in protein trafficking, Rab11a, is required for ciliogenesis in hair cells during development in mice. In addition, in the absence of Rab11a, stereocilia bundles lost their cohesion and integrity, and mice are deaf. These data indicate an essential role of protein trafficking in the formation of hair cell mechanotransduction apparatus, implicating a role of Rab11a or protein trafficking in linking the cilia and polarity regulatory components with the molecular machinery in building the co-hesive and precisely shaped stereocilia bundles.