Clarin-1 acts as a modulator of mechanotransduction activity and presynaptic ribbon assembly

Ogun, Oluwatobi; Zallocchi, Marisa

doi:10.1085/jgp.1446oia51

Cited by 6 publications

(8 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given the reported function of clarin‐1 in maturation of IHC ribbon synapses (Zallocchi et al , ; Ogun & Zallocchi, ), we also used immunolabelling to examine the ribbon synapse in clarinet cochlear whole mounts. In P21 apical‐coil IHCs, a similar number of pre‐synaptic ribbons (Ribeye‐positive puncta) and post‐synaptic densities (GluR2‐positive puncta) were observed in Clrn2 +/+ and Clrn2 clarinet /+ control and Clrn2 clarinet / clarinet mutant mice (Fig G and H).…”

Section: Resultsmentioning

confidence: 99%

Clarin‐2 is essential for hearing by maintaining stereocilia integrity and function

et al. 2019

View full text Add to dashboard Cite

Hearing relies on mechanically gated ion channels present in the actin‐rich stereocilia bundles at the apical surface of cochlear hair cells. Our knowledge of the mechanisms underlying the formation and maintenance of the sound‐receptive structure is limited. Utilizing a large‐scale forward genetic screen in mice, genome mapping and gene complementation tests, we identified Clrn2 as a new deafness gene. The Clrn2clarinet/clarinet mice (p.Trp4* mutation) exhibit a progressive, early‐onset hearing loss, with no overt retinal deficits. Utilizing data from the UK Biobank study, we could show that CLRN2 is involved in human non‐syndromic progressive hearing loss. Our in‐depth morphological, molecular and functional investigations establish that while it is not required for initial formation of cochlear sensory hair cell stereocilia bundles, clarin‐2 is critical for maintaining normal bundle integrity and functioning. In the differentiating hair bundles, lack of clarin‐2 leads to loss of mechano‐electrical transduction, followed by selective progressive loss of the transducing stereocilia. Together, our findings demonstrate a key role for clarin‐2 in mammalian hearing, providing insights into the interplay between mechano‐electrical transduction and stereocilia maintenance.

show abstract

Section: Resultsmentioning

confidence: 99%

Clarin‐2 is essential for hearing by maintaining stereocilia integrity and function

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Proteomics analysis of CLRN1-interacting proteins suggests that CLRN1 is associated with the regulation of actin homeostasis. 7 Consistently, studies of CLRN1-deficient mouse [7][8][9] and zebrafish 10 indicate structural and functional defects in the stereocilia: actin-filled membrane structures responsible for the mechanosensation of auditory hair cells. Furthermore, recent study using CLRN1-deficient zebrafish suggests that CLRN1 is also potentially involved in synaptic transmission by hair cells.…”

mentioning

confidence: 79%

“…Recent studies suggest that CLRN1 is possibly involved in the function of synapses in auditory hair cells of mouse and zebrafish. 10 Other studies, however, failed to detect such synapse defects, 8,9,46 and instead demonstrated roles of CLRN1 in stereocilia of hair cells that are not present in photoreceptor neurons. For the studies of Usher syndromes, the major challenges are that sensory deficits are observed in retina and cochlea which have no apparent functional similarities, and that animal models which demonstrate retinal deficits are often missing.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Impairment of Vision in a Mouse Model of Usher Syndrome Type III

Guo

Lee

Ropelewski

et al. 2016

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…Based on its expression sites and animal models, several theories about its function have been postulated (Ogun and Zallocchi 2014), but one of the most prevailing is that clarin-1 plays a role in the cochlear and photoreceptor synapses (Adato et al 2002, Geng et al 2009, Zallocchi et al 2009, Ogun and Zallocchi 2014).…”

Section: Genes Involved In Usher Syndrome Type 3 Clrn1mentioning

confidence: 99%

Therapeutic approaches and development of genomic diagnostic tools for Usher syndrome

García¹

View full text Add to dashboard Cite

Gracias también a todo mi grupillo de Philly que tan rápida y cálidamente me recibieron en su cuadrilla. En especial a Berta y Álvaro, por allanarme tanto el camino; y a Alba y Vicky, que desde el primer minuto os desvivisteis por que aprovechara al máximo mi estancia. Many thanks to Dr. Hakonarson and all the CAG members for allowing me the opportunity to learn from such a proficient and nice team during those six months. No me olvido tampoco del resto de amigos que, sólo con interesarse por mi trabajo o darme apoyo moral, también me ayudado durante estos años. Y, por supuesto, gracias a mi familia. A mis abuelos, porque sé que muchas de mis capacidades las he heredado de ellos, y porque sé la enorme ilusión que les habría hecho ser partícipes de este momento. En especial, a mi abuelo Jesús, quien sembró mi interés por la investigación y a quien le hubiese entusiasmado saber que finalmente desarrollé su profesión platónica. A Adrián, mil gracias (y me quedo corta). Es una gran suerte poder compartir las ilusiones e inquietudes del gremio con mi compañero de vida y de vocación. Gracias por sacarme de tantos apuros, porque literalmente sin ti me habría estancado. Gracias por escucharme cuando he necesitado desahogarme, por animarme y aconsejarme, y por disfrutar con mis éxitos. Gracias, en suma, por ser mi cómplice en todo. Gracias, de manera muy profunda, a mis padres, a quienes dedico esta tesis. Por innumerables motivos que, a fin de cuentas y de forma desvirtuada, se reducen a una esencia: por apoyarme siempre en todo, por las oportunidades que me habéis dado, por educarme como lo habéis hecho, y por vuestro desmedido cariño. Porque si he llegado hasta aquí, ha sido por vosotros, y porque si soy quien soy, es por vosotros. Gracias papá, gracias mamá, por ser como sois. Finalmente, mi más sincera gratitud a todos los pacientes y sus familiares que han participado en los estudios. Al fin y al cabo, todo esto es por vosotros. Gracias por vuestra confianza. Quiero creer que nuestro empeño, si no el de otros, acabará traduciéndose en una solución.

show abstract

Clarin-1 acts as a modulator of mechanotransduction activity and presynaptic ribbon assembly

Cited by 6 publications

References 41 publications

Clarin‐2 is essential for hearing by maintaining stereocilia integrity and function

Clarin‐2 is essential for hearing by maintaining stereocilia integrity and function

Impairment of Vision in a Mouse Model of Usher Syndrome Type III

Therapeutic approaches and development of genomic diagnostic tools for Usher syndrome

Contact Info

Product

Resources

About