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Islet primary cilia motility controls insulin secretion

Jung Hoon Cho, Zipeng A. Li, Lifei Zhu, Brian D. Muegge, Henry F. Roseman, Toby Utterback, Louis G. Woodhams, Philip V. Bayly, View ORCID ProfileJing W. Hughes
doi: https://doi.org/10.1101/2021.12.14.472629
Jung Hoon Cho
1Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
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Zipeng A. Li
1Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
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Lifei Zhu
1Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
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Brian D. Muegge
1Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
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Henry F. Roseman
1Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
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Toby Utterback
2Department of Mechanical Engineering and Materials Science, Washington University McKelvey School of Engineering, 1 Brookings Drive, Saint Louis, MO, USA
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Louis G. Woodhams
2Department of Mechanical Engineering and Materials Science, Washington University McKelvey School of Engineering, 1 Brookings Drive, Saint Louis, MO, USA
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Philip V. Bayly
2Department of Mechanical Engineering and Materials Science, Washington University McKelvey School of Engineering, 1 Brookings Drive, Saint Louis, MO, USA
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Jing W. Hughes
1Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
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  • ORCID record for Jing W. Hughes
  • For correspondence: jing.hughes@wustl.edu
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ABSTRACT

Primary cilia are specialized cell-surface organelles that mediate sensory perception and, in contrast to motile cilia and flagella, are thought to lack motility function. Here we show that primary cilia in pancreatic beta cells exhibit movement that is required for glucose-dependent insulin secretion. Beta cell cilia contain motor proteins conserved from those found in classic motile cilia, and their 3D motion is dynein-driven and dependent on ATP and glucose metabolism. Inhibition of cilia motion blocks beta cell calcium influx and insulin secretion. Beta cells from humans with type 2 diabetes have altered expression of cilia motility genes. Our findings redefine primary cilia as dynamic structures possessing both sensory and motile function and establish that pancreatic beta cell cilia movement plays a critical role in controlling insulin secretion.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 14, 2021.
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Islet primary cilia motility controls insulin secretion
Jung Hoon Cho, Zipeng A. Li, Lifei Zhu, Brian D. Muegge, Henry F. Roseman, Toby Utterback, Louis G. Woodhams, Philip V. Bayly, Jing W. Hughes
bioRxiv 2021.12.14.472629; doi: https://doi.org/10.1101/2021.12.14.472629
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Islet primary cilia motility controls insulin secretion
Jung Hoon Cho, Zipeng A. Li, Lifei Zhu, Brian D. Muegge, Henry F. Roseman, Toby Utterback, Louis G. Woodhams, Philip V. Bayly, Jing W. Hughes
bioRxiv 2021.12.14.472629; doi: https://doi.org/10.1101/2021.12.14.472629

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