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

Wei Liu,Annelies Schrott-Fischer,Hubert Löwenheim,Helge Rask-Andersen,Peter A Santi,Rudolf Glueckert

doi:10.1007/s00441-018-2793-2

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.

Highlights

TMPRSS3 (Trans-membrane Serine Protease 3) is a type II trans-membrane serine protease that belongs to a class of membrane-bound proteolytic enzymes whose genes are expressed in several tissues, including the fetal inner ear (Guipponi et al 2002, 2008; Fasquelle et al 2011)
We have studied TMPRSS3 protein expression in the human cochlea with super-resolution for the first time via structured illumination fluorescent microscopy (SR-SIM) by using a polyclonal antibody developed against a recombinant protein hosted in the rabbit
Parvalbumin was immunostained in the cytoplasm of both inner hair cells (IHC) and outer hair cells (OHC) and helped to localize the TMPRSS3 protein within hair cells (Liu et al 2009)

Summary

Introduction

TMPRSS3 (Trans-membrane Serine Protease 3) is a type II trans-membrane serine protease that belongs to a class of membrane-bound proteolytic enzymes whose genes are expressed in several tissues, including the fetal inner ear (Guipponi et al 2002, 2008; Fasquelle et al 2011). These membrane proteases are involved in diverse cellular activities. According to Guipponi et al (2008) and Fasquelle et al (2011), TMPRSS3 is located and functionally active in the endoplasmic reticulum

Methods

Results

Conclusion