RRC ID 76642
Author Shimada K, Park S, Oura S, Noda T, Morohoshi A, Matzuk MM, Ikawa M.
Title TSKS localizes to nuage in spermatids and regulates cytoplasmic elimination during spermiation.
Journal Proc Natl Acad Sci U S A
Abstract Spermatozoa have a streamlined shape to swim through the oviduct to fertilize oocytes. To become svelte spermatozoa, spermatid cytoplasm must be eliminated in several steps including sperm release, which is part of spermiation. Although this process has been well observed, the molecular mechanisms that underlie it remain unclear. In male germ cells, there are membraneless organelles called nuage, which are observed by electron microscopy in various forms of dense material. Reticulated body (RB) and chromatoid body remnant (CR) are two types of nuage in spermatids, but the functions of both are unknown. Using CRISPR/Cas9 technology, we deleted the entire coding sequence of testis-specific serine kinase substrate (TSKS) in mice and demonstrate that TSKS is essential for male fertility through the formation of both RB and CR, prominent sites of TSKS localization. Due to the lack of TSKS-derived nuage (TDN), the cytoplasmic contents cannot be eliminated from spermatid cytoplasm in Tsks knockout mice, resulting in excess residual cytoplasm with an abundance of cytoplasmic materials and inducing an apoptotic response. In addition, ectopic expression of TSKS in cells results in formation of amorphous nuage-like structures; dephosphorylation of TSKS helps to induce nuage, while phosphorylation of TSKS blocks the formation. Our results indicate that TSKS and TDN are essential for spermiation and male fertility by eliminating cytoplasmic contents from the spermatid cytoplasm.
Volume 120(11)
Pages e2221762120
Published 2023-3-14
DOI 10.1073/pnas.2221762120
PMID 36881620
PMC PMC10242716
MeSH Animals Cytoplasm Cytoskeletal Proteins* / genetics Cytosol Germ Cell Ribonucleoprotein Granules* Male Mice Mice, Knockout Phosphoproteins* / genetics Semen Spermatids*
IF 9.412
DNA material pCAG1.1-Tsks/1D4 (RDB19972) pCAG1.1-Myc/TSSK1 (RDB19973) pCAG1.1-TSSK2/3xFLAG (RDB19974) pCAG1.1-HA/Ppp1cc2 (RDB19975)