Microtubule-associated protein 1 A and tubby act independently in regulating the localization of stereocilin to the tips of inner ear hair cell stereocilia

Song Yi Youn, Hyehyun Min, Se Rok Jeong, Jiahn Lee, Seok Jun Moon, Jinwoong Bok, Chul Hoon Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Tubby mice exhibit hearing impairment due to the loss of stereocilin from the tip regions that connect the tallest stereocilia of the outer hair cells (OHCs) to the tectorial membrane. Stereocilin is an essential stereociliary protein in the OHCs, the mutation of which in humans causes autosomal recessive non-syndromic deafness. Map1a is a modifier of tubby hearing (moth1), and its wild-type allele, rather than the moth1 allele from the C57BL/6 J strain, restores stereocilin localization to the stereocilia and rescues the hearing impairment of tubby mice. The mechanism by which MAP1A accomplishes this is unclear, partly due to ambiguity regarding whether the tubby mutation is a true null. We therefore generated Tub-null (Tub−/−) mice by deleting exon 3 and found that they exhibit hearing impairment like that of tubby mice, suggesting the tubby mutation is a loss-of-function mutation with regard to hearing. When we crossed Tub−/− mice with AKR mice that have wild-type Map1a alleles, we found that wild-type MAP1A restores stereocilin localization to the tips of stereocilia and rescues hearing impairment. These data suggest MAP1A does not require interaction with tubby protein in maintaining stereocilin at the tips of stereocilia and that OHCs use two independent molecules—MAP1A and tubby—to doubly ensure proper stereocilin localization.

Original languageEnglish
Article number80
JournalMolecular brain
Volume15
Issue number1
DOIs
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (NRF-2018R1A5A2025079, NRF-2019R1A2C3002354 to C.H.K.; NRF-2016R1A5A2008630 to S.J.M and J.B) and by a faculty research grant of Yonsei University College of Medicine (6-2017-0166).

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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