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 rib...

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Autores: Haro, Carmen, Uribe, Mary Luz, Quereda, Cristina, Cruces, Jesús, Martín-Nieto, José
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/681574
Acceso en línea:http://hdl.handle.net/10486/681574
Access Level:acceso abierto
Palabra clave:Dystroglycanopathies
Retina
mRNA
FKRP
Genes
Medicina
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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, JoséDystroglycanopathiesRetinamRNAFKRPGenesMedicinaPurpose: 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 neuronsThis 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)Molecular VisionDepartamento de BioquímicaFacultad de MedicinaInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)20182018-01-20research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/681574reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6815742026-06-23T12:46:27Z
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
Dystroglycanopathies
Retina
mRNA
FKRP
Genes
Medicina
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 Departamento de Bioquímica
Facultad de Medicina
Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
dc.subject.none.fl_str_mv Dystroglycanopathies
Retina
mRNA
FKRP
Genes
Medicina
topic Dystroglycanopathies
Retina
mRNA
FKRP
Genes
Medicina
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. 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
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-20
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/681574
url http://hdl.handle.net/10486/681574
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Molecular Vision
publisher.none.fl_str_mv Molecular Vision
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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