C2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane

Hwang, Jae Yeon; Wang, Huafeng; Lu, Yonggang; Ikawa, Masahito; Chung, Jin‐Ho

doi:10.1016/j.celrep.2021.110226

Cited by 28 publications

(44 citation statements)

References 54 publications

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“…4f ), the TRIM69 distribution is fragmented, resembling previously reported results for other known CatSper subunits 8 , 12 . Additional recent studies from our and another lab, also support physical association of C2CD6 and TRIM69 with the CatSper complex, including visualizing a quadrilinear distribution of C2CD6 along mouse sperm flagella 15 , 30 and showing co-immunoprecipitation of TRIM69 with C2CD6 15 . MS analysis of purified CatSper complexes also identified C2CD6 as one of the top high-confidence proteins 18 .…”

Section: Resultssupporting

confidence: 67%

“…4d , Supplementary Fig. 2f, g ) 15 , specifically to four nanodomains along the flagella as seen by 3D SIM imaging of TRIM69 (Fig. 4e ).…”

Section: Resultsmentioning

confidence: 81%

“…Among these candidates, we proposed that the wing structure—obviously seen extracellularly (Fig. 3f , red arrowheads) next to the tetrameric channel—might consist of SLCO6C1, because it is not only a rodent-specific but also multi-pass TM protein, whereas FANCM, C2CD6 and TRIM69 are cytoplasmic proteins conserved in both mice and humans 12 , 15 , 24 . We generated a SLCO6C1 antibody that was able to detect recombinant SLCO6C1 by Western immunoblots (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Up to now, deletions or mutations of all the reported pore-forming or other TM subunits results in the loss of the entire CatSper channel complex in the sperm flagella in mice 6 . Super-resolution light microscopy showed that the CatSper channel complex is restricted to four linear compartments within the flagellar membrane in both mouse 8 , 12 , 14 , 15 and human sperm 8 , 16 , generating a unique longitudinal signaling nanodomain in each flagellar quadrant. Genetic evidence 8 , 12 , 14 and molecular imaging of sperm distributed along the female tract 17 suggested that this unique arrangement is essential for Ca 2+ signaling and sperm hyperactivation for successful fertilization, highlighting physiological relevance of the spatial organization.…”

Section: Introductionmentioning

confidence: 99%

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3D structure and in situ arrangements of CatSper channel in the sperm flagellum

et al. 2022

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The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway. Here, we applied cryo-electron tomography to visualize the higher-order organization of the native CatSper complex in intact mammalian sperm. The repeating CatSper units form long zigzag-rows along mouse and human sperm flagella. Above each tetrameric channel pore, most of the extracellular domains form a canopy that interconnects to a zigzag-shaped roof. Murine CatSper contains an additional wing-structure connected to the tetrameric channel. The intracellular domains link two neighboring channels to a diagonal array, suggesting a dimer formation. Fitting of an atomic model of isolated monomeric CatSper to the in situ map reveals supramolecular interactions and assembly of the CatSper complex. Loss of EFCAB9-CATSPERζ alters the architecture and interactions of the channels, resulting in fragmentation and misalignment of the zigzag-rows and disruption of flagellar movement in Efcab9−/− sperm. This work offers unique insights into the structural basis for understanding CatSper regulation of sperm motility.

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Section: Resultssupporting

confidence: 67%

“…4d , Supplementary Fig. 2f, g ) 15 , specifically to four nanodomains along the flagella as seen by 3D SIM imaging of TRIM69 (Fig. 4e ).…”

Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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3D structure and in situ arrangements of CatSper channel in the sperm flagellum

et al. 2022

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“…Calcium influx is mainly driven by sperm-specific pH sensitive voltage-gated Ca 2+ channels (CatSper) [ 26 , 27 ]. Due to their biological relevance for male fertility, the structure, localization, types, expression, and regulation mechanisms of CatSper channels have been extensively investigated [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. It is, nevertheless, worth noting that the sperm plasma membrane also has other channels, such as Ca 2+ transporters, which participate in the calcium rise during sperm capacitation (e.g., Ca 2+ -ATPases; [ 36 , 37 ]; transient-receptor potential (TRP) channels [ 38 , 39 ]; Na + /Ca 2+ exchangers (NCX) [ 37 , 40 ]; voltage-gated Ca 2+ channels (Ca V ) [ 41 ]; and cyclic nucleotide-gated (CNG) channels [ 42 ]).…”

Section: Introductionmentioning

confidence: 99%

A Review on the Role of Bicarbonate and Proton Transporters during Sperm Capacitation in Mammals

Delgado-Bermúdez

Yeste

Bonet

et al. 2022

IJMS

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Alkalinization of sperm cytosol is essential for plasma membrane hyperpolarization, hyperactivation of motility, and acrosomal exocytosis during sperm capacitation in mammals. The plasma membrane of sperm cells contains different ion channels implicated in the increase of internal pH (pHi) by favoring either bicarbonate entrance or proton efflux. Bicarbonate transporters belong to the solute carrier families 4 (SLC4) and 26 (SLC26) and are currently grouped into Na+/HCO3− transporters and Cl−/HCO3− exchangers. Na+/HCO3− transporters are reported to be essential for the initial and fast entrance of HCO3− that triggers sperm capacitation, whereas Cl−/HCO3− exchangers are responsible for the sustained HCO3− entrance which orchestrates the sequence of changes associated with sperm capacitation. Proton efflux is required for the fast alkalinization of capacitated sperm cells and the activation of pH-dependent proteins; according to the species, this transport can be mediated by Na+/H+ exchangers (NHE) belonging to the SLC9 family and/or voltage-gated proton channels (HVCN1). Herein, we discuss the involvement of each of these channels in sperm capacitation and the acrosome reaction.

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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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C2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane

Cited by 28 publications

References 54 publications

3D structure and in situ arrangements of CatSper channel in the sperm flagellum

3D structure and in situ arrangements of CatSper channel in the sperm flagellum

A Review on the Role of Bicarbonate and Proton Transporters during Sperm Capacitation in Mammals

Human globozoospermia‐related genes and their role in acrosome biogenesis

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