Journal article
Ganglioside GM3 is essential for the structural integrity and function of cochlear hair cells
Human molecular genetics, v 24(10), pp 2796-2807
15 May 2015
PMID: 25652401
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
GM3 synthase (ST3GAL5) is the first biosynthetic enzyme of a- and b-series gangliosides. Patients with GM3 synthase deficiency suffer severe neurological disability and deafness. Eight children (ages 4.1 ± 2.3 years) homozygous for ST3GAL5 c.694C>T had no detectable GM3 (a-series) or GD3 (b-series) in plasma. Their auditory function was characterized by the absence of middle ear muscle reflexes, distortion product otoacoustic emissions and cochlear microphonics, as well as abnormal auditory brainstem responses and cortical auditory-evoked potentials. In St3gal5(-/-) mice, stereocilia of outer hair cells showed signs of degeneration as early as postnatal Day 3 (P3); thereafter, blebs devoid of actin or tubulin appeared at the region of vestigial kinocilia, suggesting impaired vesicular trafficking. Stereocilia of St3gal5(-/-) inner hair cells were fused by P17, and protein tyrosine phosphatase receptor Q, normally linked to myosin VI at the tapered base of stereocilia, was maldistributed along the cell membrane. B4galnt1(-/-) (GM2 synthase-deficient) mice expressing only GM3 and GD3 gangliosides had normal auditory structure and function. Thus, GM3-dependent membrane microdomains might be essential for the proper organization and maintenance of stereocilia in auditory hair cells.
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Details
- Title
- Ganglioside GM3 is essential for the structural integrity and function of cochlear hair cells
- Creators
- Misato Yoshikawa - Fukuoka UniversityShinji Go - Tohoku Medical and Pharmaceutical UniversityShun-ichi Suzuki - Division of Glycopathology, Institute of Molecular Biomembranes and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Aoba-ku, Sendai, Miyagi 981-8558, JapanAkemi Suzuki - Tokai UniversityYukio Katori - Tohoku UniversityThierry Morlet - DuPont (United States)Steven M Gottlieb - Alfred I. duPont Hospital for ChildrenMichihiro Fujiwara - Fukuoka UniversityKatsunori Iwasaki - Fukuoka UniversityKevin A Strauss - Clinic for Special ChildrenJin-ichi Inokuchi - Division of Glycopathology, Institute of Molecular Biomembranes and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Aoba-ku, Sendai, Miyagi 981-8558, Japan, jin@tohoku-pharm.ac.jp
- Publication Details
- Human molecular genetics, v 24(10), pp 2796-2807
- Grant note
- P20 RR020173 / NCRR NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Audiology - Distance
- Web of Science ID
- WOS:000355326800009
- Scopus ID
- 2-s2.0-84929773630
- Other Identifier
- 991022168372404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Genetics & Heredity