Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss
<p dir="ltr">Age-related hearing loss (ARHL) is the most common sensory deficit in the elderly. The disease has a multifactorial etiology with both environmental and genetic factors involved being largely unknown. SLC7A8/SLC3A2 heterodimer is a neutral amino acid exchanger. Here, we...
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , , , |
| منشور في: |
2018
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| _version_ | 1864513510841516032 |
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| author | Meritxell Espino Guarch (18810097) |
| author2 | Mariona Font-Llitjós (562770) Silvia Murillo-Cuesta (519611) Ekaitz Errasti- Murugarren (18810100) Adelaida M Celaya (18810103) Giorgia Girotto (149894) Dragana Vuckovic (491541) Massimo Mezzavilla (535235) Clara Vilches (794255) Susanna Bodoy (18810106) Ignasi Sahún (18810109) Laura González (4708861) Esther Prat (794256) Antonio Zorzano (35886) Mara Dierssen (51655) Isabel Varela-Nieto (186892) Paolo Gasparini (139832) Manuel Palacín (5649286) Virginia Nunes (40884) |
| author2_role | author author author author author author author author author author author author author author author author author author |
| author_facet | Meritxell Espino Guarch (18810097) Mariona Font-Llitjós (562770) Silvia Murillo-Cuesta (519611) Ekaitz Errasti- Murugarren (18810100) Adelaida M Celaya (18810103) Giorgia Girotto (149894) Dragana Vuckovic (491541) Massimo Mezzavilla (535235) Clara Vilches (794255) Susanna Bodoy (18810106) Ignasi Sahún (18810109) Laura González (4708861) Esther Prat (794256) Antonio Zorzano (35886) Mara Dierssen (51655) Isabel Varela-Nieto (186892) Paolo Gasparini (139832) Manuel Palacín (5649286) Virginia Nunes (40884) |
| author_role | author |
| dc.creator.none.fl_str_mv | Meritxell Espino Guarch (18810097) Mariona Font-Llitjós (562770) Silvia Murillo-Cuesta (519611) Ekaitz Errasti- Murugarren (18810100) Adelaida M Celaya (18810103) Giorgia Girotto (149894) Dragana Vuckovic (491541) Massimo Mezzavilla (535235) Clara Vilches (794255) Susanna Bodoy (18810106) Ignasi Sahún (18810109) Laura González (4708861) Esther Prat (794256) Antonio Zorzano (35886) Mara Dierssen (51655) Isabel Varela-Nieto (186892) Paolo Gasparini (139832) Manuel Palacín (5649286) Virginia Nunes (40884) |
| dc.date.none.fl_str_mv | 2018-03-13T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.7554/elife.31511 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Mutations_in_L-type_amino_acid_transporter-2_support_SLC7A8_as_a_novel_gene_involved_in_age-related_hearing_loss/26020609 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Chemical sciences Medicinal and biomolecular chemistry Age-related hearing loss SLC7A8 protein Genetics Inner ear damage Hearing impairment Genetic mutations Protein function |
| dc.title.none.fl_str_mv | Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Age-related hearing loss (ARHL) is the most common sensory deficit in the elderly. The disease has a multifactorial etiology with both environmental and genetic factors involved being largely unknown. SLC7A8/SLC3A2 heterodimer is a neutral amino acid exchanger. Here, we demonstrated that SLC7A8 is expressed in the mouse inner ear and that its ablation resulted in ARHL, due to the damage of different cochlear structures. These findings make SLC7A8 transporter a strong candidate for ARHL in humans. Thus, a screening of a cohort of ARHL patients and controls was carried out revealing several variants inSLC7A8, whose role was further investigated by in vitro functional studies. Significant decreases in SLC7A8 transport activity was detected for patient’s variants (p.Val302Ile, p.Arg418His, p.Thr402Met and p.Val460Glu) further supporting a causative role for SLC7A8 in ARHL. Moreover, our preliminary data suggest that a relevant proportion of ARHL cases could be explained by SLC7A8 mutations.</p><h2>Other Information</h2><p dir="ltr">Published in: eLife<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.7554/elife.31511" target="_blank">https://dx.doi.org/10.7554/elife.31511</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_0c03d2060b05686c7f190152c9737bd6 |
| identifier_str_mv | 10.7554/elife.31511 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26020609 |
| publishDate | 2018 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing lossMeritxell Espino Guarch (18810097)Mariona Font-Llitjós (562770)Silvia Murillo-Cuesta (519611)Ekaitz Errasti- Murugarren (18810100)Adelaida M Celaya (18810103)Giorgia Girotto (149894)Dragana Vuckovic (491541)Massimo Mezzavilla (535235)Clara Vilches (794255)Susanna Bodoy (18810106)Ignasi Sahún (18810109)Laura González (4708861)Esther Prat (794256)Antonio Zorzano (35886)Mara Dierssen (51655)Isabel Varela-Nieto (186892)Paolo Gasparini (139832)Manuel Palacín (5649286)Virginia Nunes (40884)Biomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsChemical sciencesMedicinal and biomolecular chemistryAge-related hearing lossSLC7A8 proteinGeneticsInner ear damageHearing impairmentGenetic mutationsProtein function<p dir="ltr">Age-related hearing loss (ARHL) is the most common sensory deficit in the elderly. The disease has a multifactorial etiology with both environmental and genetic factors involved being largely unknown. SLC7A8/SLC3A2 heterodimer is a neutral amino acid exchanger. Here, we demonstrated that SLC7A8 is expressed in the mouse inner ear and that its ablation resulted in ARHL, due to the damage of different cochlear structures. These findings make SLC7A8 transporter a strong candidate for ARHL in humans. Thus, a screening of a cohort of ARHL patients and controls was carried out revealing several variants inSLC7A8, whose role was further investigated by in vitro functional studies. Significant decreases in SLC7A8 transport activity was detected for patient’s variants (p.Val302Ile, p.Arg418His, p.Thr402Met and p.Val460Glu) further supporting a causative role for SLC7A8 in ARHL. Moreover, our preliminary data suggest that a relevant proportion of ARHL cases could be explained by SLC7A8 mutations.</p><h2>Other Information</h2><p dir="ltr">Published in: eLife<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.7554/elife.31511" target="_blank">https://dx.doi.org/10.7554/elife.31511</a></p>2018-03-13T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.7554/elife.31511https://figshare.com/articles/journal_contribution/Mutations_in_L-type_amino_acid_transporter-2_support_SLC7A8_as_a_novel_gene_involved_in_age-related_hearing_loss/26020609CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260206092018-03-13T09:00:00Z |
| spellingShingle | Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss Meritxell Espino Guarch (18810097) Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Chemical sciences Medicinal and biomolecular chemistry Age-related hearing loss SLC7A8 protein Genetics Inner ear damage Hearing impairment Genetic mutations Protein function |
| status_str | publishedVersion |
| title | Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss |
| title_full | Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss |
| title_fullStr | Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss |
| title_full_unstemmed | Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss |
| title_short | Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss |
| title_sort | Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss |
| topic | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Chemical sciences Medicinal and biomolecular chemistry Age-related hearing loss SLC7A8 protein Genetics Inner ear damage Hearing impairment Genetic mutations Protein function |