Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Mutations that Affect Channel Opening of Innexin Hemichannels in the C. elegans Gonad

Version 1 : Received: 1 November 2020 / Approved: 3 November 2020 / Online: 3 November 2020 (14:01:49 CET)

How to cite: Starich, T.; Greenstein, D. Mutations that Affect Channel Opening of Innexin Hemichannels in the C. elegans Gonad. Preprints 2020, 2020110151 (doi: 10.20944/preprints202011.0151.v1). Starich, T.; Greenstein, D. Mutations that Affect Channel Opening of Innexin Hemichannels in the C. elegans Gonad. Preprints 2020, 2020110151 (doi: 10.20944/preprints202011.0151.v1).

Abstract

In C. elegans, gap junctions couple cells of the somatic gonad with the germline to support germ cell proliferation and gametogenesis. We previously characterized a strong loss-of-function mutation (T239I) affecting the second extracellular loop (EL2) of the somatic INX-8 hemichannel subunit. These mutant hemichannels form non-functional gap junctions with germline-expressed innexins. Here we describe the characterization of mutations that restore germ cell proliferation in the T239I EL2 mutant background. We recovered 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 hemichannels that support germline proliferation but cause the demise of somatic sheath cells. Phenotypic analyses of three other suppressors reveal an equivalency in the rescue of germline proliferation and comparable delays in gametogenesis but a graded rescue of fertility. These latter mutations may be useful to probe interactions with the biochemical pathways that produce the molecules transiting through soma-germline gap junctions.

Subject Areas

gap junctions; innexins; soma-germline interactions

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