The perinuclear theca protein Calicin helps shape the sperm head and maintain the nuclear structure in mice

Xiao-zhen, Zhang; Wei, Lin-Lin; Jin, Hui-Juan; Zhang, Xiaohui; Chen, Su‐Ren

doi:10.1016/j.celrep.2022.111049

Cited by 32 publications

(56 citation statements)

References 46 publications

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“…3 A, red arrowheads), we analyzed the localization of other calyx specific proteins, such as CCIN and CapZα3. In Cylc 1 −/y and Cylc2 +/- sperm, CCIN localization remained unchanged, being present in the calyx and in the ventral portion of PT as described previously 7 . However, in Cylc2 −/- sperm, CCIN localizes to the tail or in random parts of the sperm head (Fig.…”

Section: Resultssupporting

confidence: 74%

“…This dynamic localization pattern of Cylicins has been described in human, boar and bovine sperm as well 2, 14, 15 . Interestingly, other PT enriched proteins CCIN 12, 30, 7 and CPβ3/CPα3 move in the similar manner across PT during spermiogenesis and are present in the calyx of mature sperm of various mammalian species. This co-localization suggests the potential interaction between calyx proteins.…”

Section: Discussionmentioning

confidence: 94%

“…(A) Testis weight [mg] and sperm count (x10 7 ) of WT, Cylc1 −/y , Cylc2 +/- , Cylc2 −/- , Cylc1 −/y Cylc2 +/- and Cylc1 −/y Cylc2 −/- males. Mean values +/- SD are shown; block dots represent data points for individual males.…”

Section: Resultsmentioning

confidence: 99%

“…The loss of Cylicins caused acrosome detachment from NE starting from cap phase of the acrosome biogenesis. Interestingly, loss of CCIN results in similar loosening of the acroplaxome from the outer nuclear membrane 7 . Calicin is shown to be necessary for the IAM-PT-NE complex by establishing bidirectional connections.…”

Section: Discussionmentioning

confidence: 97%

“…Proteomic analyses using murine and bovine PT extracts revealed 500-800 different proteins, highlighting its high molecular complexity 6, 7 . Apart from cytoskeletal proteins, signaling molecules and several de novo synthesized core histones were identified.…”

Section: Introductionmentioning

confidence: 99%

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Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human

Schneider

Kovacevic

Mayer

et al. 2022

Preprint

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Cylicins are testis specific proteins which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 (Cylc1/CYLC1) and the autosomal Cylicin 2 (Cylc2/CYLC2) genes have been identified. Cylicins are cytoskeletal proteins with an overall positive charge due to lysine-rich repeats. While Cylicins have been localized in the acrosomal region of round spermatids, they resemble a major component of the calyx within the perinuclear theca at the posterior part of mature sperm nuclei. However, the role of Cylicins during spermiogenesis has not yet been investigated. Here, we applied CRISPR/Cas9 mediated gene-editing in zygotes to establish Cylc1- and Cylc2-deficient mouse lines as a model to study the function of these proteins. Cylc1-deficiency resulted in male subfertility whereas Cylc2-/-, Cylc1-/y Cylc2+/-, and Cylc1-/y Cylc2-/- males were infertile. Phenotypical characterization revealed that loss of Cylicins prevents proper calyx assembly during spermiogenesis. This results in decreased epididymal sperm counts, impaired shedding of excess cytoplasm, and severe structural malformations, ultimately resulting in impaired sperm motility. Furthermore, exome sequencing identified an infertile man with a hemizygous variant in CYLC1 and a heterozygous variant in CYLC2, displaying morphological abnormalities of the sperm including the absence of the acrosome. Thus, our study highlights the relevance and importance of Cylicins for spermiogenic remodeling and male fertility in human and mouse, and provides the basis for further studies on unraveling the complex molecular interactions between perinuclear theca proteins required during spermiogenesis.

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Section: Resultssupporting

confidence: 74%

Section: Discussionmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human

Schneider

Kovacevic

Mayer

et al. 2022

Preprint

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Human globozoospermia‐related genes and their role in acrosome biogenesis

Moreno

2022

WIREs Mechanisms of Disease

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The mammalian acrosome is a secretory vesicle attached to the sperm nucleus whose fusion with the overlying plasma membrane is required to achieve fertilization. Acrosome biogenesis starts during meiosis, but it lasts through the entire process of haploid cell differentiation (spermiogenesis). Acrosome biogenesis is a stepwise process that involves membrane traffic from the Golgi apparatus, but it also seems that the lysosome/endosome system participates in this process. Defective sperm head morphology is accompanied by defective acrosome shape and function, and patients with these characteristics are infertile or subfertile. The most extreme case of acrosome biogenesis failure is globozoospermia syndrome, which is primarily characterized by the presence of round‐headed spermatozoa without acrosomes with cytoskeleton defects around the nucleus and infertility. Several genes participating in acrosome biogenesis have been uncovered using genetic deletions in mice, but only a few of them have been found to be deleted or modified in patients with globozoospermia. Understanding acrosome biogenesis is crucial to uncovering the molecular basis of male infertility and developing new diagnostic tools and assisted reproductive technologies that may help infertile patients through more effective treatment techniques. This article is categorized under: Reproductive System Diseases > Environmental Factors Infectious Diseases > Stem Cells and Development Reproductive System Diseases > Molecular and Cellular Physiology

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