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Article

A Limited and Diverse Set of Suppressor Mutations Restore Function to INX-8 Mutant Hemichannels in the Caenorhabditis elegans Somatic Gonad

Department Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA
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Biomolecules 2020, 10(12), 1655; https://doi.org/10.3390/biom10121655
Received: 1 November 2020 / Revised: 5 December 2020 / Accepted: 8 December 2020 / Published: 10 December 2020
(This article belongs to the Special Issue Connexins, Innexins, and Pannexins: From Biology to Clinical Targets)
In Caenorhabditis elegans, gap junctions couple cells of the somatic gonad with the germline to support germ cell proliferation and gametogenesis. A strong loss-of-function mutation (T239I) affects the second extracellular loop (EL2) of the somatic INX-8 hemichannel subunit. These mutant hemichannels form non-functional gap junctions with germline-expressed innexins. We conducted a genetic screen for suppressor mutations that restore germ cell proliferation in the T239I mutant background and isolated seven intragenic mutations, located in diverse domains of INX-8 but not the EL domains. These second-site mutations compensate for the original channel defect to varying degrees, from nearly complete wild-type rescue, to partial rescue of germline proliferation. One suppressor mutation (E350K) supports the innexin cryo-EM structural model that the channel pore opening is surrounded by a cytoplasmic dome. Two suppressor mutations (S9L and I36N) may form leaky channels that support germline proliferation but cause the demise of somatic sheath cells. Phenotypic analyses of three of the suppressors reveal an equivalency in the rescue of germline proliferation and comparable delays in gametogenesis but a graded rescue of fertility. The mutations described here may be useful for elucidating the biochemical pathways that produce the active biomolecules transiting through soma–germline gap junctions. View Full-Text
Keywords: gap junctions; innexins; soma–germline interactions gap junctions; innexins; soma–germline interactions
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MDPI and ACS Style

Starich, T.; Greenstein, D. A Limited and Diverse Set of Suppressor Mutations Restore Function to INX-8 Mutant Hemichannels in the Caenorhabditis elegans Somatic Gonad. Biomolecules 2020, 10, 1655. https://doi.org/10.3390/biom10121655

AMA Style

Starich T, Greenstein D. A Limited and Diverse Set of Suppressor Mutations Restore Function to INX-8 Mutant Hemichannels in the Caenorhabditis elegans Somatic Gonad. Biomolecules. 2020; 10(12):1655. https://doi.org/10.3390/biom10121655

Chicago/Turabian Style

Starich, Todd; Greenstein, David. 2020. "A Limited and Diverse Set of Suppressor Mutations Restore Function to INX-8 Mutant Hemichannels in the Caenorhabditis elegans Somatic Gonad" Biomolecules 10, no. 12: 1655. https://doi.org/10.3390/biom10121655

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