Expression of trans-membrane serine protease 3 (TMPRSS3) in the human organ of Corti

Abstract

TMPRSS3 (Trans-membrane Serine Protease 3) is a type II trans-membrane serine protease that has proteolytic activity essential for hearing. Mutations in the gene cause non-syndromic autosomal recessive deafness (DFNB8/10) in humans. Knowledge about its cellular distribution in the human inner ear may increase our understanding of its physiological role and involvement in deafness, ultimately leading to therapeutic interventions. In this study, we used super-resolution structured illumination microscopy for the first time together with transmission electron microscopy to localize the TMPRSS3 protein in the human organ of Corti. Archival human cochleae were dissected out during petroclival meningioma surgery. Microscopy with Zeiss LSM710 microscope achieved a lateral resolution of approximately 80 nm. TMPRSS3 was found to be associated with actin in both inner and outer hair cells. TMPRSS3 was located in cell surface-associated cytoskeletal bodies (surfoskelosomes) in inner and outer pillar cells and Deiters cells and in subcuticular organelles in outer hair cells. Our results suggest that TMPRSS3 proteolysis is linked to hair cell sterociliary mechanics and to the actin/microtubule networks that support cell motility and integrity.Electronic supplementary materialThe online version of this article (10.1007/s00441-018-2793-2) contains supplementary material, which is available to authorized users.

Human Inner Ear Immune Activity: A Super-Resolution Immunohistochemistry Study

“…Table 1 shows the antibodies used in the present study. The immunohistochemistry procedures performed on the sections have been described in previous publications (19–21). Briefly, the slide-mounted sections were incubated with an antibody solution under a humidified atmosphere at 4°C for 20 h. After rinsing with PBS three times for 5 min each, the sections were incubated with secondary antibodies conjugated to Alexa Fluor 488, 555, and 647 (Molecular Probes, Carlsbad, CA, USA), counter-stained with the nuclear stain 4′,6-diamidino-2-phenylindole dihydro-chloride (DAPI; Thermo Fisher Scientific, Waltham, MA, USA) for 5–7 min, rinsed with PBS (3 × 5 min), mounted with ProLong® Gold Antifade Mountant (Thermo Fisher Scientific), and covered with the specified cover glass required for optically matching the SIM objectives.…”

Auditory synaptopathy, auditory neuropathy, and cochlear implantation

“…The function of the protein encoded by TMPRSS3 , transmembrane serine protease 3, is unknown. However, multiple studies have shown the protein to be expressed in inner and outer hair cells as well as the spiral ganglion, including in dissected human temporal bones . A recent study showed that TMPRSS3 is expressed highly in type II spiral ganglion neurons in mice .…”

Human cochlear microanatomy – an electron microscopy and super-resolution structured illumination study and review

“…In humans, TEM shows a dense meshwork associated with cell junctional complexes at the plasma membrane referred to as surfoskelosomes [13]. These are located in the pillar heads and foot (basal bodies) that contain organized actin and are closely associated with microtubules [16]. Deiters' cells also express organized actin in basal bodies.…”

“…An intriguing association was found between actin and the enzyme TMPRSS3, a type II trans-membrane serine protease , [16]. Several mutations in the TMPRSS3 gene on chromosome 21q22.3 cause autosomal recessive non-syndromic deafness (DFNB8/10) with varied phenotypic expression [23,24].…”