TY - JOUR
T1 - Zinc transporters ZIPT-2.4 and ZIPT-15 are required for normal C. elegans fecundity
AU - Sue, Aaron C.
AU - Wignall, Sarah M.
AU - Woodruff, Teresa K
AU - O’Halloran, Thomas V.
N1 - Funding Information:
Research in this study was supported by National Institute of Health grants R01GM115848 (TKW and TVO), U54CA193419 (TVO), R01GM038784 (TVO), and R01GM124354 (SMW).
Funding Information:
The authors would like to thank Dr. Mendoza for many helpful discussions regarding C. elegans zinc transporter biology, R. Brielmann and the Morimoto lab for instruction and use of their microinjection setup, and Dr. Zhang, Dr. Crombie, and the Andersen lab for assistance and use of their worm plate imaging setup. Microscopy was performed at the Biological Imaging Facility at Northwestern University (RRID:SCR_017767), graciously supported by the Chemistry for Life Processes Institute, the NU Office for Research, and the Department of Molecular Biosciences. Dr. Hornick and Dr. Antonova were helpful in resolving microscopy issues and recommending imaging parameters.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/6
Y1 - 2022/6
N2 - Purpose: The requirement of zinc for the development and maturation of germ lines and reproductive systems is deeply conserved across evolution. The nematode Caenorhabditis elegans offers a tractable platform to study the complex system of distributing zinc to the germ line. We investigated several zinc importers to investigate how zinc transporters play a role in the reproductive system in nematodes, as well as establish a platform to study zinc transporter biology in germline and reproductive development. Methods: Previous high throughput transcriptional datasets as well as phylogenetic analysis identified several putative zinc transporters that have a function in reproduction in worms. Phenotypic analysis of CRISPR-generated knockouts and tags included characterization of offspring output, gonad development, and protein localization. Light and immunofluorescence microscopy allowed for visualization of physiological and molecular effects of zinc transporter mutations. Results: Disruption of two zinc transporters, ZIPT-2.4 and ZIPT-15, was shown to lead to defects in reproductive output. A mutation in zipt-2.4 has subtle effects on reproduction, while a mutation in zipt-15 has a clear impact on gonad and germline development that translates into a more pronounced defect in fecundity. Both transporters have germline expression, as well as additional expression in other cell types. Conclusions: Two ZIP-family zinc transporter orthologs of human ZIP6/10 and ZIP1/2/3 proteins are important for full reproductive fecundity and participate in development of the gonad. Notably, these zinc transporters are present in gut and reproductive tissues in addition to the germ line, consistent with a complex zinc trafficking network important for reproductive success.
AB - Purpose: The requirement of zinc for the development and maturation of germ lines and reproductive systems is deeply conserved across evolution. The nematode Caenorhabditis elegans offers a tractable platform to study the complex system of distributing zinc to the germ line. We investigated several zinc importers to investigate how zinc transporters play a role in the reproductive system in nematodes, as well as establish a platform to study zinc transporter biology in germline and reproductive development. Methods: Previous high throughput transcriptional datasets as well as phylogenetic analysis identified several putative zinc transporters that have a function in reproduction in worms. Phenotypic analysis of CRISPR-generated knockouts and tags included characterization of offspring output, gonad development, and protein localization. Light and immunofluorescence microscopy allowed for visualization of physiological and molecular effects of zinc transporter mutations. Results: Disruption of two zinc transporters, ZIPT-2.4 and ZIPT-15, was shown to lead to defects in reproductive output. A mutation in zipt-2.4 has subtle effects on reproduction, while a mutation in zipt-15 has a clear impact on gonad and germline development that translates into a more pronounced defect in fecundity. Both transporters have germline expression, as well as additional expression in other cell types. Conclusions: Two ZIP-family zinc transporter orthologs of human ZIP6/10 and ZIP1/2/3 proteins are important for full reproductive fecundity and participate in development of the gonad. Notably, these zinc transporters are present in gut and reproductive tissues in addition to the germ line, consistent with a complex zinc trafficking network important for reproductive success.
KW - Caenorhabditis elegans
KW - Fecundity
KW - Germline development
KW - Germline gene expression
KW - Zinc transporter
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U2 - 10.1007/s10815-022-02495-z
DO - 10.1007/s10815-022-02495-z
M3 - Article
C2 - 35501415
AN - SCOPUS:85129298990
SN - 1058-0468
VL - 39
SP - 1261
EP - 1276
JO - Journal of Assisted Reproduction and Genetics
JF - Journal of Assisted Reproduction and Genetics
IS - 6
ER -