Universität zu Köln

Li, Mengnan, Nishio, Shin-ya ORCID: 0000-0001-6640-2297, Naruse, Chie, Riddell, Meghan, Sapski, Sabrina, Katsuno, Tatsuya, Hikita, Takao, Mizapourshafiyi, Fatemeh, Smith, Fiona M., Cooper, Leanne T., Lee, Min Goo ORCID: 0000-0001-7436-012X, Asano, Masahide, Boettger, Thomas ORCID: 0000-0003-4280-8449, Krueger, Marcus ORCID: 0000-0003-2008-4582, Wietelmann, Astrid, Graumann, Johannes ORCID: 0000-0002-3015-5850, Day, Bryan W., Boyd, Andrew W., Offermanns, Stefan, Kitajiri, Shin-ichiro, Usami, Shin-ichi and Nakayama, Masanori (2020). Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome. Nat. Commun., 11 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results in hearing loss. Here we identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4. EphA2 forms a protein complex with pendrin controlling pendrin localization, which is disrupted in some pathogenic forms of pendrin. Moreover, point mutations leading to amino acid substitution in the EPHA2 gene are identified from patients bearing mono-allelic mutation of SLC26A4. Ephrin-B2 binds to EphA2 triggering internalization with pendrin inducing EphA2 autophosphorylation weakly. The identified EphA2 mutants attenuate ephrin-B2- but not ephrin-A1-induced EphA2 internalization with pendrin. Our results uncover an unexpected role of the Eph/ephrin system in epithelial function.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Li, Mengnan UNSPECIFIED UNSPECIFIED UNSPECIFIED Nishio, Shin-ya UNSPECIFIED orcid.org/0000-0001-6640-2297 UNSPECIFIED Naruse, Chie UNSPECIFIED UNSPECIFIED UNSPECIFIED Riddell, Meghan UNSPECIFIED UNSPECIFIED UNSPECIFIED Sapski, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED Katsuno, Tatsuya UNSPECIFIED UNSPECIFIED UNSPECIFIED Hikita, Takao UNSPECIFIED UNSPECIFIED UNSPECIFIED Mizapourshafiyi, Fatemeh UNSPECIFIED UNSPECIFIED UNSPECIFIED Smith, Fiona M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cooper, Leanne T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, Min Goo UNSPECIFIED orcid.org/0000-0001-7436-012X UNSPECIFIED Asano, Masahide UNSPECIFIED UNSPECIFIED UNSPECIFIED Boettger, Thomas UNSPECIFIED orcid.org/0000-0003-4280-8449 UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Wietelmann, Astrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Graumann, Johannes UNSPECIFIED orcid.org/0000-0002-3015-5850 UNSPECIFIED Day, Bryan W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boyd, Andrew W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Offermanns, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kitajiri, Shin-ichiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Usami, Shin-ichi UNSPECIFIED UNSPECIFIED UNSPECIFIED Nakayama, Masanori UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-341084
DOI:	10.1038/s41467-020-15198-9
Journal or Publication Title:	Nat. Commun.
Volume:	11
Number:	1
Date:	2020
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOTYPE-PHENOTYPE CORRELATION; HEARING-LOSS; SYNDROME GENE; PDS GENE; VESTIBULAR AQUEDUCT; RECEPTORS; EPHRIN-B2; EXPRESSION; MORPHOGENESIS; ENLARGEMENT Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/34108