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Common Piezo1 allele in African populations causes xerocytosis and attenuates Plasmodium infection

Shang Ma, Stuart Cahalan, Rakhee Lohia, Gregory LaMonte, Weizheng Zeng, Swetha Murthy, Emma Paytas, Nathan D. Grubaugh, Ramya Gamini, Laurence Berry, Viktor Lukacs, Tess Whitwam, Meaghan Loud, Andrew I. Su, Kristian G. Andersen, Elizabeth A. Winzeler, Eric Honore, Kai Wengelnik, Ardem Patapoutian
doi: https://doi.org/10.1101/159830
Shang Ma
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
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Stuart Cahalan
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
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Rakhee Lohia
2DIMNP, CNRS, INSERM, Univ Montpellier, Montpellier, France.
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Gregory LaMonte
3Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, California, USA.
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Weizheng Zeng
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
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Swetha Murthy
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
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Emma Paytas
3Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, California, USA.
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Nathan D. Grubaugh
4Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.
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Ramya Gamini
5Department of Integrative, Structural and Computational Biology, Scripps Research Institute, La Jolla, California, USA.
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  • For correspondence: rgamini@scripps.edu
Laurence Berry
2DIMNP, CNRS, INSERM, Univ Montpellier, Montpellier, France.
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Viktor Lukacs
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
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Tess Whitwam
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
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Meaghan Loud
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
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Andrew I. Su
5Department of Integrative, Structural and Computational Biology, Scripps Research Institute, La Jolla, California, USA.
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Kristian G. Andersen
4Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.
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Elizabeth A. Winzeler
3Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, California, USA.
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Eric Honore
6+, Valbonne, France
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Kai Wengelnik
2DIMNP, CNRS, INSERM, Univ Montpellier, Montpellier, France.
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Ardem Patapoutian
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
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  • For correspondence: ardem@scripps.edu
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Abstract

Hereditary xerocytosis (HX) is thought to be a rare genetic condition characterized by red blood cell (RBC) dehydration with mild hemolysis. Gain-of-function (GOF) mutations in mechanosensitive Piezo1 ion channels are identified in HX patients. RBC dehydration is linked to reduced Plasmodium infection rates in vitro. We engineered a Piezo1 mouse model of HX and show that Plasmodium infection fails to cause experimental cerebral malaria in these mice. Furthermore, we identified a novel GOF human Piezo1 variant, E756del, present in a third of African population. Remarkably, RBCs from individuals carrying this allele are dehydrated and protected against Plasmodium infection in vitro. The presence of an HX-causing Piezo1 mutation at such high frequencies in African population is surprising, and suggests an association with malaria resistance.

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Posted July 06, 2017.
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Common Piezo1 allele in African populations causes xerocytosis and attenuates Plasmodium infection
Shang Ma, Stuart Cahalan, Rakhee Lohia, Gregory LaMonte, Weizheng Zeng, Swetha Murthy, Emma Paytas, Nathan D. Grubaugh, Ramya Gamini, Laurence Berry, Viktor Lukacs, Tess Whitwam, Meaghan Loud, Andrew I. Su, Kristian G. Andersen, Elizabeth A. Winzeler, Eric Honore, Kai Wengelnik, Ardem Patapoutian
bioRxiv 159830; doi: https://doi.org/10.1101/159830
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Common Piezo1 allele in African populations causes xerocytosis and attenuates Plasmodium infection
Shang Ma, Stuart Cahalan, Rakhee Lohia, Gregory LaMonte, Weizheng Zeng, Swetha Murthy, Emma Paytas, Nathan D. Grubaugh, Ramya Gamini, Laurence Berry, Viktor Lukacs, Tess Whitwam, Meaghan Loud, Andrew I. Su, Kristian G. Andersen, Elizabeth A. Winzeler, Eric Honore, Kai Wengelnik, Ardem Patapoutian
bioRxiv 159830; doi: https://doi.org/10.1101/159830

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