Molecular Neurobiology

, Volume 55, Issue 8, pp 6518–6532 | Cite as

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

  • 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 BokEmail author
  • Un-Kyung KimEmail author


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.


Exoc5 Exocyst Cochlea Spiral ganglion Hearing loss 



Inner hair cells


Spiral ganglion neurons


Embryonic day


Recombinant adeno-associated virus


AAV serotype 2 and a capsid from AAV serotype 1


Codon-improved Cre recombinase


Enhanced green fluorescent protein


Genome copies per milliliter


Normal goat serum


0.1% Triton X-100 in 1× PBS




Optimal cutting temperature compound




Room temperature




Auditory brainstem response


Postnatal day


Tucker Davis Technology


Sound pressure level


Scanning electron microscopy


Reverse-transcription polymerase chain reaction


Terminal deoxynucleotidyl transferase dUTP nick end labeling


Outer hair cells


c-Jun N-terminal kinase


Tight junction



We thank Dr. Lin Gan for Gfi1Cre/+ mice. The UAB P30 Hepatorenal Fibrocystic Disease Core Center is gratefully acknowledged for generating the Exoc5f/f mice. This work was supported by the National Research Foundation of Korea Grant 2014M3A9D5073865 (to J.B. and U.K.K.), 2017R1C1B2009705 (to J.I.B), and 2017R1A2B3009133 (to J.B.), and by the Yonsei University Future-leading Research Initiative (2015-22-0058). This work was also supported in part by grants from the VA (Merit Award I01 BX000820 to J.H.L) and NIH (P30DK074038 to J.H.L) in the USA.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

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Authors and Affiliations

  1. 1.Department of Biology, College of Natural SciencesKyungpook National UniversityDaeguRepublic of Korea
  2. 2.School of Life Sciences, BK21 Plus KNU Creative BioResearch GroupKyungpook National UniversityDaeguRepublic of Korea
  3. 3.Department of Aroma-applied IndustryDaegu Haany UniversityGyeongsanRepublic of Korea
  4. 4.Department of MedicineMedical University of South CarolinaCharlestonUSA
  5. 5.Department of AnatomyYonsei University College of MedicineSeoulRepublic of Korea
  6. 6.BK21PLUS Project for Medical ScienceYonsei University College of MedicineSeoulRepublic of Korea
  7. 7.Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of MedicineUniversity of Hawaii at ManoaHonoluluUSA
  8. 8.Department of MedicineRalph H. Johnson Veterans Affairs Medical CenterCharlestonUSA
  9. 9.Department of Otorhinolaryngology-Head and Neck Surgery, School of MedicineKyungpook National UniversityDaeguRepublic of Korea
  10. 10.Department of OtorhinolaryngologyYonsei University College of MedicineSeoulRepublic of Korea

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