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

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

doi:10.1007/s00441-018-2793-2

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

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

Otolaryngology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Pages (from-to)	445-456
Number of pages	12
Journal	Cell and Tissue Research
Volume	372
Issue number	3
DOIs	https://doi.org/10.1007/s00441-018-2793-2
State	Published - Jun 1 2018

Bibliographical note

Funding Information:
Our research is part of the European Community Research: Human stem cell applications for the treatment of hearing loss, grant agreement no. 603029; project acronym: OTOSTEM. Private funds from Börje Runögård and David Giertz, Sweden also provided financial support. We are grateful to SciLife Laboratories and the Biovis Facility, Uppsala University, Dag Hammarskjölds v 14B, 751 85 Uppsala, Sweden (http://biovis.uu.se/) for providing SR-SIM microscope equipment and personal support during the entire study. We thank Karin Lodin for skillful artwork.

Funding Information:
Acknowledgments Our research is part of the European Community Research: Human stem cell applications for the treatment of hearing loss, grant agreement no. 603029; project acronym: OTOSTEM. Private funds from Börje Runögård and David Giertz, Sweden also provided financial support. We are grateful to SciLife Laboratories and the Biovis Facility, Uppsala University, Dag Hammarskjölds v 14B, 751 85 Uppsala, Sweden (http://biovis.uu.se/) for providing SR-SIM microscope equipment and personal support during the entire study. We thank Karin Lodin for skillful artwork.

Publisher Copyright:
© 2018, The Author(s).

Keywords

Cochlea
Human
Immunohistochemistry
Super-resolution structured illumination microscopy (SR-SIM)
Trans-membrane Serine Protease 3 (TMPRSS3)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00441-018-2793-2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949142

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title = "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.",

keywords = "Cochlea, Human, Immunohistochemistry, Super-resolution structured illumination microscopy (SR-SIM), Trans-membrane Serine Protease 3 (TMPRSS3)",

author = "Wei Liu and Hubert L{\"o}wenheim and Santi, {Peter A.} and Rudolf Glueckert and Annelies Schrott-Fischer and Helge Rask-Andersen",

note = "Funding Information: Our research is part of the European Community Research: Human stem cell applications for the treatment of hearing loss, grant agreement no. 603029; project acronym: OTOSTEM. Private funds from B{\"o}rje Run{\"o}g{\aa}rd and David Giertz, Sweden also provided financial support. We are grateful to SciLife Laboratories and the Biovis Facility, Uppsala University, Dag Hammarskj{\"o}lds v 14B, 751 85 Uppsala, Sweden (http://biovis.uu.se/) for providing SR-SIM microscope equipment and personal support during the entire study. We thank Karin Lodin for skillful artwork. Funding Information: Acknowledgments Our research is part of the European Community Research: Human stem cell applications for the treatment of hearing loss, grant agreement no. 603029; project acronym: OTOSTEM. Private funds from B{\"o}rje Run{\"o}g{\aa}rd and David Giertz, Sweden also provided financial support. We are grateful to SciLife Laboratories and the Biovis Facility, Uppsala University, Dag Hammarskj{\"o}lds v 14B, 751 85 Uppsala, Sweden (http://biovis.uu.se/) for providing SR-SIM microscope equipment and personal support during the entire study. We thank Karin Lodin for skillful artwork. Publisher Copyright: {\textcopyright} 2018, The Author(s).",

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AU - Liu, Wei

AU - Löwenheim, Hubert

AU - Santi, Peter A.

AU - Glueckert, Rudolf

AU - Schrott-Fischer, Annelies

AU - Rask-Andersen, Helge

N1 - Funding Information: Our research is part of the European Community Research: Human stem cell applications for the treatment of hearing loss, grant agreement no. 603029; project acronym: OTOSTEM. Private funds from Börje Runögård and David Giertz, Sweden also provided financial support. We are grateful to SciLife Laboratories and the Biovis Facility, Uppsala University, Dag Hammarskjölds v 14B, 751 85 Uppsala, Sweden (http://biovis.uu.se/) for providing SR-SIM microscope equipment and personal support during the entire study. We thank Karin Lodin for skillful artwork. Funding Information: Acknowledgments Our research is part of the European Community Research: Human stem cell applications for the treatment of hearing loss, grant agreement no. 603029; project acronym: OTOSTEM. Private funds from Börje Runögård and David Giertz, Sweden also provided financial support. We are grateful to SciLife Laboratories and the Biovis Facility, Uppsala University, Dag Hammarskjölds v 14B, 751 85 Uppsala, Sweden (http://biovis.uu.se/) for providing SR-SIM microscope equipment and personal support during the entire study. We thank Karin Lodin for skillful artwork. Publisher Copyright: © 2018, The Author(s).

PY - 2018/6/1

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N2 - 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.

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KW - Immunohistochemistry

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

Abstract

Bibliographical note

Keywords

UN SDGs

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