USH2A is a Meissner's corpuscle protein necessary for normal vibration sensing in mice and humans.

Fecha de publicación: 01/01/2021 Fecha Ahead of Print: 01/12/2020

Autores de IIS La Fe

Gema García García

Autor
José María Millán Salvador

Autor

Participantes ajenos a IIS La Fe

Schwaller F
Bégay V
Taberner FJ
Moshourab R
McDonald B
Docter T
Kühnemund J
Ojeda-Alonso J
Paricio-Montesinos R
Lechner SG
Poulet JFA
Lewin GR

Grupos

Biomedicina Molecular, Celular y Genómica

Leader

José María Millán Salvador
Unidad mixta de investigación en enfermedades raras (CIPF)

Leader

José María Millán Salvador

Abstract

Fingertip mechanoreceptors comprise sensory neuron endings together with specialized skin cells that form the end-organ. Exquisitely sensitive, vibration-sensing neurons are associated with Meissner's corpuscles in the skin. In the present study, we found that USH2A, a transmembrane protein with a very large extracellular domain, was found in terminal Schwann cells within Meissner's corpuscles. Pathogenic USH2A mutations cause Usher's syndrome, associated with hearing loss and visual impairment. We show that patients with biallelic pathogenic USH2A mutations also have clear and specific impairments in vibrotactile touch perception, as do mutant mice lacking USH2A. Forepaw rapidly adapting mechanoreceptors innervating Meissner's corpuscles, recorded from Ush2a -/- mice, showed large reductions in vibration sensitivity. However, the USH2A protein was not found in sensory neurons. Thus, loss of USH2A in corpuscular end-organs reduced mechanoreceptor sensitivity as well as vibration perception. Thus, a tether-like protein is required to facilitate detection of small-amplitude vibrations essential for the perception of fine-grained tactile surfaces.

Datos de la publicación

ISSN/ISSNe:: 1097-6256, 1546-1726
Tipo:: Article
Páginas:: 74-81
DOI:: 10.1038/s41593-020-00751-y
Factor de Impacto:: 12,017 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

Schwaller F:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany
Bégay V:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany
García-García G:: Instituto de Investigación. Research Group on Molecular, Cellular and Genomic Biomedicine Health Research, Institute La Fe and Joint Unit for Rare Diseases CIPF-IIS La Fe, Valencia, Spain

Center for Biomedical Network Research on Rare Diseases, Institute of Health Carlos III, Madrid, Spain
Taberner FJ:: Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany

Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Alicante, Spain
Moshourab R:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Department of Anesthesiology and Operative Intensive Care Medicine, Campus Virchow Klinikum and Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany

Department of Anesthesiology, Helios Klinikum Erfurt, Erfurt, Germany
McDonald B:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany
Docter T:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Department of Molecular and Cellular Biology at Life Sciences Addition, University of California at Berkeley, Berkeley, CA, USA
Kühnemund J:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany
Ojeda-Alonso J:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany
Paricio-Montesinos R:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Neuroscience Research Center, Charité-Universitätsmedizin, Berlin, Germany
Lechner SG:: Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany
Poulet JFA:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Neuroscience Research Center, Charité-Universitätsmedizin, Berlin, Germany
Millan JM:: Instituto de Investigación. Research Group on Molecular, Cellular and Genomic Biomedicine Health Research, Institute La Fe and Joint Unit for Rare Diseases CIPF-IIS La Fe, Valencia, Spain

Center for Biomedical Network Research on Rare Diseases, Institute of Health Carlos III, Madrid, Spain
Lewin GR:: Department of Neuroscience, Max Delbrück Center for Molecular Medicine, Berlin, Germany.

Keywords

MECHANORECEPTIVE AFFERENT UNITS; GLABROUS SKIN; MECHANOTRANSDUCTION; SENSITIVITY; INTENSITY; USHERIN; PIEZO2; CELLS; GENE

Proyectos asociados

CARACTERIZACION MOLECULAR DE PACIENTES CON SINDROME DE USHER. ESTUDIO DE LOS GENES RESPONSABLES: CDH23 Y PCDH15 Y CANDIDATOS: WHRN, CXADR Y PDZK7

Investigador Principal: JOSÉ MARÍA MILLÁN SALVADOR

PI07/0558 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2008

MOLECULAR MAECHANISMS OF RETINAL DEGENERATION IN HUMANS WITH RETINITIS PIGMENTOSA. ROLE OF INFLAMMATION, OXIDATIVE STRESS AND GLIAL ACTIVATION

CP09/00118 (MIGUEL SERVET) . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

RED DE BIOBANCOS (BIOBANCOS)

RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

CARACTERIZACION MOLECULAR EN PACIENTES CON SINDROME DE USHER TIPO I MEDIANTE LA APLICACION DE LAS TECNICAS DE SECUENCIACION Y CGH-ARRAY EN GENES RESPONSABLES Y GENES CANDIDATOS

FPU_AP2009-3344 . MINISTERIO DE EDUCACION, CULTURA Y DEPORTE; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010