Mouse DCUN1D1 (SCCRO) is required for spermatogenetic individualization Journal Article

Authors: Huang, G.; Kaufman, A. J.; Ryan, R. J. H.; Romin, Y.; Huryn, L.; Bains, S.; Manova-Todorova, K.; Morris, P. L.; Hunnicutt, G. R.; Adelman, C. A.; Petrini, J. H. J.; Ramanathan, Y.; Singh, B.
Article Title: Mouse DCUN1D1 (SCCRO) is required for spermatogenetic individualization
Abstract: Squamous cell carcinoma–related oncogene (SCCRO, also known as DCUN1D1) is a component of the E3 for neddylation. As such, DCUN1D1 regulates the neddylation of cullin family members. Targeted inactivation of DCUN1D1 in mice results in male-specific infertility. Infertility in DCUN1D1-/- mice is secondary to primary defects in spermatogenesis. Time-dam experiments mapped the onset of the defect in spermatogenesis to 5.5 to 6 weeks of age, which temporally corresponds to defects in spermiogenesis. Although the first round of spermatogenesis progressed normally, the number of spermatozoa released into the seminiferous lumen and epididymis of DCUN1D1-/- mice was significantly reduced. Spermatozoa in DCUN1D1-/- mice had multiple abnormalities, including globozoospermia, macrocephaly, and multiple flagella. Many of the malformed spermatozoa in DCUN1D1-/- mice were multinucleated, with supernumerary and malpositioned centrioles, suggesting a defect in the resolution of intercellular bridges. The onset of the defect in spermatogenesis in DCUN1D1-/-mice corresponds to an increase in DCUN1D1 expression observed during normal spermatogenesis. Moreover, consistent with its known function as a component of the E3 in neddylation, the pattern of DCUN1D1 expression temporally correlates with an increase in the neddylated cullin fraction and stage-specific increases in the total ubiquitinated protein pool in wild-type mice. Levels of neddylated Cul3 were decreased in DCUN1D1-/- mice, and ubiquitinated proteins did not accumulate during the stages in which DCUN1D1 expression peaks during spermatogenesis in wild-type mice. Combined, these findings suggest that DCUN1D1-/- mice fail to release mature spermatozoa into the seminiferous lumen, possibly due to unresolved intercellular bridges. Furthermore, the effects of DCUN1D1 on spermatogenesis likely involve its regulation of cullin-RING-ligase (CRL)–type ubiquitin E3 activity during spermiogenesis through its role in promoting Cul3 neddylation. The specific CRLs required for spermiogenesis and their protein targets require identification. © 2019 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Journal Title: PLoS ONE
Volume: 14
Issue: 1
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2019-01-17
Start Page: e0209995
Language: English
DOI: 10.1371/journal.pone.0209995
PUBMED: 30653527
PROVIDER: scopus
PMCID: PMC6336273
Notes: Export Date: 1 February 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Russell J H Ryan
    5 Ryan
  2. Bhuvanesh Singh
    217 Singh
  3. John Petrini
    83 Petrini
  4. Guochang Huang
    15 Huang
  5. Sarina Bains
    19 Bains
  6. Laryssa A Huryn
    3 Huryn
  7. Yevgeniy Romin
    16 Romin