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Asymmetrically Positioned Flagellar Control Units Regulate Human Sperm Rotation

65 Pages Posted: 6 Jun 2018 Publication Status: Published

See all articles by Melissa R. Miller

Melissa R. Miller

University of California, Berkeley - Department of Molecular and Cell Biology

Samuel J. Kenny

University of California, Berkeley - Department of Chemistry

Nadja Mannowetz

University of California, Berkeley - Department of Molecular and Cell Biology

Steven A. Mansell

University of California, Berkeley - Department of Molecular and Cell Biology

Michal Wojcik

University of California, Berkeley - Department of Chemistry

Sarah Mendoza

University of California, Berkeley - Department of Molecular and Cell Biology

Robert S. Zucker

University of California, Berkeley - Department of Molecular and Cell Biology

Ke Xu

University of California, Berkeley - Department of Chemistry

Polina V. Lishko

University of California, Berkeley - Department of Molecular and Cell Biology

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Abstract

The ability of sperm to fertilize an egg is controlled by ion channels, one of which is the pHdependent calcium channel of sperm CatSper. For CatSper to be fully activated, the cytoplasmic pH must be alkaline, which is accomplished by either proton transporters, or a faster mechanism, such as the voltage-gated proton channel Hv1. To ensure effective regulation, these channels and regulatory proteins must be tightly compartmentalized. Here, we characterize human sperm nanodomains that are comprised of Hv1, CatSper and regulatory protein ABHD2. Superresolution microscopy revealed that Hv1 forms asymmetrically positioned bilaterally distributed longitudinal lines that span the entire length of the sperm tail. Such a distribution provides a direct structural basis for the selective activation of CatSper, and subsequent flagellar rotation along the long axis that, together with hyperactivated motility, enhances sperm fertility. Indeed, Hv1 inhibition leads to a decrease in sperm rotation. Thus, sperm ion channels are organized in distinct regulatory nanodomains that control hyperactivated motility and rotation.

Suggested Citation

Miller, Melissa R. and Kenny, Samuel J. and Mannowetz, Nadja and Mansell, Steven A. and Wojcik, Michal and Mendoza, Sarah and Zucker, Robert S. and Xu, Ke and Lishko, Polina V., Asymmetrically Positioned Flagellar Control Units Regulate Human Sperm Rotation (2018). Available at SSRN: https://ssrn.com/abstract=3188435 or http://dx.doi.org/10.2139/ssrn.3188435
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Melissa R. Miller

University of California, Berkeley - Department of Molecular and Cell Biology

310 Barrows Hall
Berkeley, CA 94720
United States

Samuel J. Kenny

University of California, Berkeley - Department of Chemistry

310 Barrows Hall
Berkeley, CA 94720
United States

Nadja Mannowetz

University of California, Berkeley - Department of Molecular and Cell Biology

310 Barrows Hall
Berkeley, CA 94720
United States

Steven A. Mansell

University of California, Berkeley - Department of Molecular and Cell Biology

310 Barrows Hall
Berkeley, CA 94720
United States

Michal Wojcik

University of California, Berkeley - Department of Chemistry

310 Barrows Hall
Berkeley, CA 94720
United States

Sarah Mendoza

University of California, Berkeley - Department of Molecular and Cell Biology

310 Barrows Hall
Berkeley, CA 94720
United States

Robert S. Zucker

University of California, Berkeley - Department of Molecular and Cell Biology

310 Barrows Hall
Berkeley, CA 94720
United States

Ke Xu

University of California, Berkeley - Department of Chemistry ( email )

310 Barrows Hall
Berkeley, CA 94720
United States

Polina V. Lishko (Contact Author)

University of California, Berkeley - Department of Molecular and Cell Biology ( email )

310 Barrows Hall
Berkeley, CA 94720
United States

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