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Exocyst Complex Member EXOC5 Is Required for Survival of Hair Cells and Spiral Ganglion Neurons and Maintenance of Hearing

Authors
 Byeonghyeon Lee  ;  Jeong-In Baek  ;  Hyehyun Min  ;  Seung-Hyun Bae  ;  Kyeonghye Moon  ;  Min-A Kim  ;  Ye-Ri Kim  ;  Ben Fogelgren  ;  Joshua H. Lipschutz  ;  Kyu-Yup Lee  ;  Jinwoong Bok  ;  Un-Kyung Kim 
Citation
 MOLECULAR NEUROBIOLOGY, Vol.55 : 6518-6532, 2018 
Journal Title
 MOLECULAR NEUROBIOLOGY 
ISSN
 0893-7648 
Issue Date
2018
Keywords
Cochlea ; Exoc5 ; Exocyst ; Hearing loss ; Spiral ganglion
Abstract
The exocyst, an octameric protein complex consisting of Exoc1 through Exoc8, was first determined to regulate exocytosis by targeting vesicles to the plasma membrane in yeast to mice. In addition to this fundamental role, the exocyst complex has been implicated in other cellular processes. In this study, we investigated the role of the exocyst in cochlear development and hearing by targeting EXOC5, a central exocyst component. Deleting Exoc5 in the otic epithelium with widely used Cre lines resulted in early lethality. Thus, we generated two different inner ear-specific Exoc5 knockout models by crossing Gfi1Cre mice with Exoc5f/f mice for hair cell-specific deletion (Gfi1Cre/+;Exoc5f/f) and by in utero delivery of rAAV-iCre into the otocyst of embryonic day 12.5 for deletion throughout the otic epithelium (rAAV2/1-iCre;Exoc5f/f). Gfi1Cre/+;Exoc5f/f mice showed relatively normal hair cell morphology until postnatal day 20, after which hair cells underwent apoptosis accompanied by disorganization of stereociliary bundles, resulting in progressive hearing loss. rAAV2/1-iCre;Exoc5f/f mice exhibited abnormal neurite morphology, followed by apoptotic degeneration of spiral ganglion neurons (SGNs) and hair cells, which led to profound and early-onset hearing loss. These results demonstrate that Exoc5 is essential for the normal development and survival of cochlear hair cells and SGNs, as well as the functional maintenance of hearing.
Full Text
https://link.springer.com/article/10.1007%2Fs12035-017-0857-z
DOI
10.1007/s12035-017-0857-z
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Min, Hye Hyun(민혜현) ORCID logo https://orcid.org/0000-0001-5450-5088
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163225
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