A5055505363- Hearing, Cochlea, Tinnitus, Genetics
- Connexins and lens biology
- Retinal Development and Disorders
- Congenital heart defects research
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Hearing Loss and Rehabilitation
- Advanced biosensing and bioanalysis techniques
- Calcium signaling and nucleotide metabolism
- Biochemical Analysis and Sensing Techniques
- Neurological diseases and metabolism
- Protein Tyrosine Phosphatases
- Plant Molecular Biology Research
- Enzyme Structure and Function
- Hereditary Neurological Disorders
- RNA regulation and disease
- Nicotinic Acetylcholine Receptors Study
- Coronary Artery Anomalies
- Vestibular and auditory disorders
- Bacterial Genetics and Biotechnology
- Acoustic Wave Phenomena Research
- Phosphodiesterase function and regulation
- Chemical Synthesis and Analysis
- Peroxisome Proliferator-Activated Receptors
Institut Pasteur
2003-2020
Sorbonne Université
2012-2020
Inserm
2006-2020
Institut de la Vision
2012-2020
Ciência Viva
2020
Centre Ophtalmologique d'Imagerie et de Laser
2015-2019
Université Paris Cité
2015
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2008
Genoscope
2008
Centre National de la Recherche Scientifique
2008
The mechanisms underlying retinal dystrophy in Usher syndrome type I (USH1) remain unknown because mutant mice lacking any of the USH1 proteins-myosin VIIa, harmonin, cadherin-23, protocadherin-15, sans-do not display degeneration. We found here that, macaque photoreceptor cells, all proteins colocalized at membrane interfaces (i) between inner and outer segments rods (ii) microvillus-like calyceal processes segment basolateral region cones. This pattern, conserved humans frogs, was mediated...
Clarin-1, a tetraspan-like membrane protein defective in Usher syndrome type IIIA (USH3A), is essential for hair bundle morphogenesis auditory cells. We report new synaptic role clarin-1 mouse cells elucidated by characterization of Clrn1 total (Clrn1ex4–/–) and postnatal cell–specific conditional (Clrn1ex4fl/fl Myo15-Cre+/–) knockout mice. Clrn1ex4–/– mice were profoundly deaf, whereas Clrn1ex4fl/fl Myo15-Cre+/– displayed progressive increases hearing thresholds, with, initially, normal...
Significance Noise-induced hearing loss is a highly prevalent form of sensorineural impairment affecting individuals all ages. Noise exposure triggers rapid increase in reactive oxygen species (ROS) levels, causing oxidative damage to auditory hair cells and resulting loss. Here we describe novel mechanism protection against noise-induced cell damage. In response sound exposure, pejvakin, peroxisome-associated protein, acts as an ROS sensor recruits the autophagy machinery trigger...
The mitochondrial metalloprotease AFG3L2 assembles with the homologous protein paraplegin to form a supracomplex in charge of essential quality control within mitochondria. Mutations cause specific axonal degeneration upper motoneuron and, therefore, hereditary spastic paraplegia. Here we present two Afg3l2 murine models: newly developed null and spontaneous mutant that found carrier missense mutation. Contrasting mild late onset paraplegin-deficient mouse, models display marked impairment...
Defects of CIB2, calcium- and integrin-binding protein 2, have been reported to cause isolated deafness, DFNB48 Usher syndrome type-IJ, characterized by congenital profound balance defects blindness. We report here two new nonsense mutations (pGln12* pTyr110*) in CIB2 patients displaying nonsyndromic hearing loss, with no evidence vestibular or retinal dysfunction. Also, the generated CIB2-/- mice display an early onset deafness normal functions. In these mice, mechanoelectrical transduction...
The precise architecture of hair bundles, the arrays mechanosensitive microvilli-like stereocilia crowning auditory cells, is essential to hearing. Myosin IIIa, defective in late-onset deafness form DFNB30, has been proposed transport espin-1 tips stereocilia, thereby promoting their elongation. We show that Myo3a−/−Myo3b−/− mice lacking myosin IIIa and IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b−/− losing postnatally have normal cochlear bundles display robust mechanoelectrical...
Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy patients remains elusive. The protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base photoreceptor outer segment. We show that Xenopus tropicalis, these processes connected outer-segment membrane by links composed protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained a knockdown...
We report a consanguineous Iranian family affected by congenital profound sensorineural deafness segregating in an autosomal recessive mode. Auditory tests implicated at least cochlear defect these patients. mapped the deafness, (DFNB) locus involved linkage analysis to 4.8 Mb region chromosome 21q22.3-qter. Exclusion of DFNB8/10 gene TMPRSS3, located this chromosomal interval, led us identify new locus, DFNB98. Whole exome sequencing allowed homozygous frame-shifting mutation...
We describe a novel spontaneous autosomal recessive mutation, cervelet-4 (crv4), which arose in BALB/c strain. Mice homozygous for the mutation exhibit principally reduced body size, congenital neurological phenotype characterized by ataxic gait and intention tremor, with no gross anomalies observed brain or cerebellum, skeletal anomalies. Using linkage analysis, we mapped crv4 locus to proximal region of chromosome 10, at location Grm1 gene. Genetic complementation crosses between KO mice...
Although the d-glucarate degradation pathway is well characterized in Escherichia coli, genetic and biochemical information concerning alternative proposed Pseudomonas species Bacillus subtilis remains incomplete. Acinetobacter baylyi ADP1 a Gram-negative soil bacterium possessing able to grow using as only carbon source. Based on annotation of its sequenced genome (1Barbe V. Vallenet D. Fonknechten N. Kreimeyer A. Oztas S. Labarre L. Cruveiller Robert C. Duprat Wincker P. Ornston L.N....
cGMP is critical to a variety of cellular processes, but the available tools interfere with endogenous lack and subcellular specificity. We introduce SponGee, genetically encoded chelator this cyclic nucleotide that enables in vitro vivo manipulations single cells biochemically defined compartments. SponGee buffers physiological changes concentration various model systems while not affecting cAMP signals. provide proof-of-concept strategies by using tool highlight role signaling discrete...
Calcium is a second messenger crucial to myriad of cellular processes ranging from regulation metabolism and cell survival vesicle release motility. Current strategies directly manipulate endogenous calcium signals lack subcellular specificity. We introduce SpiCee, versatile genetically encoded chelator combining low- high-affinity sites for calcium. This scavenger enables altering signaling functions in single cells vitro vivo with biochemically controlled resolution. SpiCee paves the way...
Abstract The hair bundle of cochlear cells is the site auditory mechanoelectrical transduction. It formed by three rows stiff microvilli-like protrusions graduated heights, short, middle-sized, and tall stereocilia. In developing mature sensory cells, stereocilia are connected to each other various types fibrous links. Two unconventional cadherins, protocadherin-15 (PCDH15) cadherin-23 (CDH23), form tip-links, whose tension gates cell transduction channels. These proteins also transient...
ou non, émanant des établissements d'enseignement et de recherche français étrangers, laboratoires publics privés.
Calcium is a second messenger crucial to myriad of cellular processes ranging from regulation metabolism and cell survival vesicle release motility. Current strategies directly manipulate endogenous calcium signals lack subcellular specificity. We developed SpiCee, versatile genetically-encoded chelator combining low high affinity sites for calcium. This scavenger enables altering signaling functions in single cells vitro vivo with biochemically-controlled resolution. SpiCee paves the way...
The Paralysé mutation is a spontaneous neuromuscular mutation, first observed in 1980 at the Pasteur Institute, which transmitted by autosomal recessive par allele. Affected homozygote par/par mice rarely survive beyond 16 days of age and end their life they are emaciated completely paralyzed. Several concordant histological physiological observations indicate that mutant might be good models for studying early-onset human motor neuron diseases such as spinal muscular atrophy. Linkage...