Microtubule-associated Protein 1A is a Modifier of Tubby Hearing (moth1)

Overview

Journal Nat Genet

Specialty Genetics

Date 2002 Apr 2

PMID 11925566

Citations 35

Authors

Akihiro Ikeda

Qing Yin Zheng

Aamir R Zuberi

Kenneth R Johnson

Jurgen K Naggert

Patsy M Nishina

Affiliations

Soon will be listed here.

Abstract

Once a mutation in the gene tub was identified as the cause of obesity, retinal degeneration and hearing loss in tubby mice, it became increasingly evident that the members of the tub gene family (tulps) influence maintenance and function of the neuronal cell lineage. Suggested molecular functions of tubby-like proteins include roles in vesicular trafficking, mediation of insulin signaling and gene transcription. The mechanisms through which tub functions in neurons, however, have yet to be elucidated. Here we report the positional cloning of an auditory quantitative trait locus (QTL), the modifier of tubby hearing 1 gene (moth1), whose wildtype alleles from strains AKR/J, CAST/Ei and 129P2/OlaHsd protect tubby mice from hearing loss. Through a transgenic rescue experiment, we verified that sequence polymorphisms in the neuron-specific microtubule-associated protein 1a gene (Mtap1a) observed in the susceptible strain C57BL/6J (B6) are crucial for the hearing-loss phenotype. We also show that these polymorphisms change the binding efficiency of MTAP1A to postsynaptic density molecule 95 (PSD95), a core component in the cytoarchitecture of synapses. This indicates that at least some of the observed polymorphisms are functionally important and that the hearing loss in C57BL/6J-tub/tub (B6-tub/tub) mice may be caused by impaired protein interactions involving MTAP1A. We therefore propose that tub may be associated with synaptic function in neuronal cells.

Citing Articles

Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti.

Lindner L, Derstroff D, Oliver D, Reimann K Front Neurosci. 2023; 17:1162937.

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

Youn S, Min H, Jeong S, Lee J, Moon S, Bok J Mol Brain. 2022; 15(1):80.

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Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation.

Wang H, Gao Y, Guan J, Lan L, Yang J, Xiong W Front Cell Dev Biol. 2021; 9:647240.

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Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells.

Han W, Shin J, Ma J, Min H, Jung J, Lee J Proc Natl Acad Sci U S A. 2020; 117(20):11109-11117.

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Growth factor and receptor malfunctions associated with human genetic deafness.

Naz S, Friedman T Clin Genet. 2019; 97(1):138-155.

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