Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes

[Purpose]: Dystroglycanopathies are a heterogeneous group of recessive neuromuscular dystrophies that affect the muscle, brain and retina, and are caused by deficiencies in the O-glycosylation of α-dystroglycan. This post-translational modification is essential for the formation and maintenance of r...

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Autores: Haro, Carmen, Uribe, Mary Luz, Quereda, Cristina, Cruces, Jesús, Martín-Nieto, José
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::0381e6f6629e5ebc5bb36db4ecd49960
Acesso em linha:http://hdl.handle.net/10261/188176
Access Level:acceso abierto
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spelling Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genesHaro, CarmenUribe, Mary LuzQuereda, CristinaCruces, JesúsMartín-Nieto, José[Purpose]: Dystroglycanopathies are a heterogeneous group of recessive neuromuscular dystrophies that affect the muscle, brain and retina, and are caused by deficiencies in the O-glycosylation of α-dystroglycan. This post-translational modification is essential for the formation and maintenance of ribbon synapses in the retina. Fukutin and fukutin-related protein (FKRP) are two glycosyltransferases whose deficiency is associated with severe dystroglycanopathies. These enzymes carry out in vitro the addition of a tandem ribitol 5-phosphate moiety to the so-called core M3 phosphotrisaccharide of α-dystroglycan. However, their expression pattern and function in the healthy mammalian retina has not so far been investigated. In this work, we have addressed the expression of the FKTN (fukutin) and FKRP genes in the retina of mammals, and characterized the distribution pattern of their protein products in the adult mouse retina and the 661W photoreceptor cell line.[Methods]: By means of reverse transcription (RT)-PCR and immunoblotting, we have studied the expression at the mRNA and protein levels of the fukutin and FKRP genes in different mammalian species, from rodents to humans. Immunofluorescence confocal microscopy analyses were performed to characterize the distribution profile of their protein products in mouse retinal sections and in 661W cultured cells.[Results]: Both genes were expressed at the mRNA and protein levels in the neural retina of all mammals studied. Fukutin was present in the cytoplasmic and nuclear fractions in the mouse retina and 661W cells, and accumulated in the endoplasmic reticulum. FKRP was located in the cytoplasmic fraction in the mouse retina and concentrated in the Golgi complex. However, and in contrast to retinal tissue, FKRP additionally accumulated in the nucleus of the 661W photoreceptors.[Conclusions]: Our results suggest that fukutin and FKRP not only participate in the synthesis of O-mannosyl glycans added to α-dystroglycan in the endoplasmic reticulum and Golgi complex, but that they could also play a role, that remains to be established, in the nucleus of retinal neurons.This research was funded by a grant from the Instituto de Salud Carlos III (Spain; ref. PI15/00073), cofinanced by the European Regional Development Fund (ERDF/FEDER). Additional funding was awarded by the UA for use of technical research facilities (ref. UAUSTI16–12), diffusion of research results (ref. UADIF 16–51) and scientific productivity (ref. VIGROB-237). M.L.U. was the recipient of a predoctoral contract from the UA (ref. UAFPU2011-Y1418344V).Peer reviewedMolecular VisionInstituto de Salud Carlos IIIEuropean CommissionUniversidad Autónoma de MadridMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/188176reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::0381e6f6629e5ebc5bb36db4ecd499602026-05-22T06:33:51Z
dc.title.none.fl_str_mv Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes
title Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes
spellingShingle Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes
Haro, Carmen
title_short Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes
title_full Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes
title_fullStr Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes
title_full_unstemmed Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes
title_sort Expression in retinal neurons of fukutin and FKRP, the protein products of two dystroglycanopathy-causative genes
dc.creator.none.fl_str_mv Haro, Carmen
Uribe, Mary Luz
Quereda, Cristina
Cruces, Jesús
Martín-Nieto, José
author Haro, Carmen
author_facet Haro, Carmen
Uribe, Mary Luz
Quereda, Cristina
Cruces, Jesús
Martín-Nieto, José
author_role author
author2 Uribe, Mary Luz
Quereda, Cristina
Cruces, Jesús
Martín-Nieto, José
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
European Commission
Universidad Autónoma de Madrid
Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description [Purpose]: Dystroglycanopathies are a heterogeneous group of recessive neuromuscular dystrophies that affect the muscle, brain and retina, and are caused by deficiencies in the O-glycosylation of α-dystroglycan. This post-translational modification is essential for the formation and maintenance of ribbon synapses in the retina. Fukutin and fukutin-related protein (FKRP) are two glycosyltransferases whose deficiency is associated with severe dystroglycanopathies. These enzymes carry out in vitro the addition of a tandem ribitol 5-phosphate moiety to the so-called core M3 phosphotrisaccharide of α-dystroglycan. However, their expression pattern and function in the healthy mammalian retina has not so far been investigated. In this work, we have addressed the expression of the FKTN (fukutin) and FKRP genes in the retina of mammals, and characterized the distribution pattern of their protein products in the adult mouse retina and the 661W photoreceptor cell line.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/188176
url http://hdl.handle.net/10261/188176
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Vision
publisher.none.fl_str_mv Molecular Vision
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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