title: Ganglioside GM3 is essential for the structural integrity and function of cochlear hair cells.
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.
authors: Division of Glycopathology, Institute of Molecular Biomembranes and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Aoba-ku, Sendai, Miyagi 981-8558, Japan, Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors: Misato
authors: M
authors: Yoshikawa
authors: Division of Glycopathology, Institute of Molecular Biomembranes and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Aoba-ku, Sendai, Miyagi 981-8558, Japan.
authors: Shinji
authors: S
authors: Go
authors: Division of Glycopathology, Institute of Molecular Biomembranes and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Aoba-ku, Sendai, Miyagi 981-8558, Japan.
authors: Shun-ichi
authors: S
authors: Suzuki
authors: Institute of Glycoscience, Tokai University, Kanagawa 259-1292, Japan.
authors: Akemi
authors: A
authors: Suzuki
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, SendaiCity, Miyagi 980-8574, Japan.
authors: Yukio
authors: Y
authors: Katori
authors: Department of Biomedical Research, Nemours, Wilmington, DE 19803, USA.
authors: Thierry
authors: T
authors: Morlet
authors: Division of Pediatric Neurology, Nemours Alfred I. DuPont Hospital for Children, Wilimington, DE 19803, USA.
authors: Steven M
authors: SM
authors: Gottlieb
authors: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors: Michihiro
authors: M
authors: Fujiwara
authors: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
authors: Katsunori
authors: K
authors: Iwasaki
authors: Clinic for Special Children, Strasburg, PA 17579, USA, Biological Foundations of Behavior Program, Franklin and Marshall College, Lancaster, PA 17602, USA and Lancaster General Hospital, Lancaster, PA 17602, USA.
authors: Kevin A
authors: KA
authors: Strauss
authors: 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.
authors: Jin-ichi
authors: J
authors: Inokuchi
mesh_terms: D000818:Animals; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005679:G(M3) Ganglioside / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000502:physiology / Q000648:ultrastructure*; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020125:Mutation, Missense; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D012799:Sialyltransferases / Q000172:deficiency* / Q000235:genetics; D059547:Stereocilia / Q000648:ultrastructure*
chemical_list: D005679:G(M3) Ganglioside; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase; D012799:Sialyltransferases; C021343:haematoside synthetase
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