Ezrin regulates microvillus morphogenesis by promoting distinct activities of Eps8 proteins.

The mechanisms that regulate actin filament polymerization resulting in the morphogenesis of the brush border microvilli in epithelial cells remain unknown. Eps8, the prototype of a family of proteins capable of capping and bundling actin filaments, has been shown to bundle the microvillar actin filaments. We report that Eps8L1a, a member of the Eps8 family and a novel ezrin-interacting partner, controls microvillus length through its capping activity.

Emerging role for ERM proteins in cell adhesion and migration.

The highly related ERM (Ezrin, Radixin, Moesin) proteins provide a regulated linkage between the membrane and the underlying actin cytoskeleton. They also provide a platform for the transmission of signals in responses to extracellular cues. Studies in different model organisms and in cultured cells have highlighted the importance of ERM proteins in the generation and maintenance of specific domains of the plasma membrane.

Beta and gamma-cytoplasmic actins display distinct distribution and functional diversity.

Using newly generated monoclonal antibodies, we have compared the distribution of beta- and gamma-cytoplasmic actin in fibroblastic and epithelial cells, in which they play crucial roles during various key cellular processes. Whereas beta-actin is preferentially localized in stress fibers, circular bundles and at cell-cell contacts, suggesting a role in cell attachment and contraction, gamma-actin displays a more versatile organization, according to cell activities. In moving cells, gamma-actin is mainly organized as a meshwork in cortical and lamellipodial structures, suggesting a role in cell motility; in stationary cells, gamma-actin is also recruited into stress fibers.

Shroom2, a myosin-VIIa- and actin-binding protein, directly interacts with ZO-1 at tight junctions.

Defects in myosin VIIa lead to developmental anomalies of the auditory and visual sensory cells. We sought proteins interacting with the myosin VIIa tail by using the yeast two-hybrid system. Here, we report on shroom2, a submembranous PDZ domain-containing protein that is associated with the tight junctions in multiple embryonic and adult epithelia.

Initial characterization of kinocilin, a protein of the hair cell kinocilium.

A subtracted library prepared from vestibular sensory areas [Nat. Genet. 26 (2000) 51] was used to identify a 960bp murine transcript preferentially expressed in the inner ear and testis.

Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22.

A 3,673-bp murine cDNA predicted to encode a glycosylphosphatidylinositol-anchored protein of 1,088 amino acids was isolated during a study aimed at identifying transcripts specifically expressed in the inner ear. This inner ear-specific protein, otoancorin, shares weak homology with megakaryocyte potentiating factor/mesothelin precursor. Otoancorin is located at the interface between the apical surface of the inner ear sensory epithelia and their overlying acellular gels.

Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus.

Hearing impairment affects about 1 in 1,000 children at birth. Approximately 70 loci implicated in non-syndromic forms of deafness have been reported in humans and 24 causative genes have been identified (see also http://www.uia.

Effect of the serotonin agonist 8-OH-DPAT on the sensorimotor system of the rat.

8-Hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT, 2 mg/kg) is used to induce perseverative behavior in rats in a T-maze as a model for obsessive-compulsive disorder (OCD). Using the open-field test, radiant heat test, and the test with von Frey filaments, we examined whether alterations in sensorimotor functioning could contribute to the perseverative tendencies in this model by measuring differences in left versus right hind paw reactions after 8-OH-DPAT administration (2 mg/kg, sc). Also, the effect of repeated 8-OH-DPAT administration on sensorimotor functioning was tested every third day.

Twister mutant mice are defective for otogelin, a component specific to inner ear acellular membranes.

Deafness is a common sensory defect in human. Our understanding of the molecular bases of this pathology comes from the study of a few genes that have been identified in human and/or in mice. Indeed, deaf mouse mutants are good models for studying and identifying genes involved in human hereditary hearing loss.

Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.

Usher syndrome (USH) is a clinically and genetically heterogeneous autosomal recessive disorder in which sensorineural hearing loss is associated with retinitis pigmentosa. Usher syndrome type 1, the most severe form, is characterized by profound congenital deafness, vestibular dysfunction, and prepubertal onset of retinitis pigmentosa. Six different USH1 genes have so far been mapped, of which two have already been identified.

A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.

Usher syndrome type 1 (USH1) is an autosomal recessive sensory defect involving congenital profound sensorineural deafness, vestibular dysfunction and blindness (due to progressive retinitis pigmentosa)1. Six different USH1 loci have been reported. So far, only MYO7A (USH1B), encoding myosin VIIA, has been identified as a gene whose mutation causes the disease.

The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord and muscular atrophy. SMA is caused by alterations to the survival of motor neuron (SMN) gene, the function of which has hitherto been unclear. Here, we present immunoblot analyses showing that normal SMN protein expression undergoes a marked decay in the postnatal period compared with fetal development.