CRISPs Function to Boost Sperm Power Output and Motility

Gaikwad, Avinash; Nandagiri, Ashwin; Potter, David; Nosrati, Reza; O’Connor, Anne E; Jadhav, Sameer; Soria, Julio; Prabhakar, Ranganathan

doi:10.3389/fcell.2021.693258

Cited by 8 publications

(3 citation statements)

References 55 publications

(105 reference statements)

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“…[ 28b ] The underlying intracellular mechanism to achieve this 3D flagellar beating dynamics is also similar to the complex activation mechanism of the dynein motors which is potentially responsible for sperm‐hyperactivated motility, [ 28 ] and may underpin a new strategy for sperm to attach/detach from the epithelial tissue particularly in the of isthmus region [ 43 ] by regulating the out‐of‐plane component of the flagellar wave indicated by the increasing curvature in the midpiece region. Using a tethered cell is a powerful and practical approach for studying flagellar development and function (in sperm and other flagellated microswimmers), genetic causes of infertility, and the transcriptional and translational control of germ‐cell‐expressed genes, [ 13c,42,44 ] and our 3D reconstruction approach provides new opportunities in this area. The 3D reconstruction technique that has been developed and presented in this paper is relevant to study the motility behavior of single‐flagellated eukaryotic cells broadly which possess similar 9+2 axoneme structure.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the time-averaged torsion along the flagellum (Figure 5b and Figure S12 (Supporting Information)) indicates a sharp peak in the midpiece region (at S < 0.2), considerably contributing to the nonplanar nature of the flagellar wave in the 3D space. These results may suggest a spatially abrupt transduction of the dynein motor signals along the flagellum to potentially achieve a rapid change in the flagellar waveform in 3D space [40] -potentially via a rapid signal transduction mechanism involving ion gating [40,41] and cysteinerich secretory proteins [42] similar to what is required for sperm hyperactivation. [28] With respect to in vivo locomotion, our findings indicate the importance of capturing the full flagellar waveform in 3D to completely describe sperm swimming behavior.…”

Section: Flagellar Waveform Is Weakly Nonplanar and Ambidextrous In N...mentioning

confidence: 99%

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Unraveling the Kinematics of Sperm Motion by Reconstructing the Flagellar Wave Motion in 3D

et al. 2022

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The flagellar wave originates from the 9+2 axoneme structure at the central core of the flagellum, where nine pairs of outer microtubule doublets are mechanically linked to a central pair. [2] The sequential sliding of the nine outer microtubules via dynein arms over the neighboring doublet bends the flagellum in 3D to produce a flagellar waveform. [3] This beating behavior is self-regulatory in nature, triggered by the combined activity of dynein motors. [3a,4] Several regulation mechanisms have been suggested to control the flagellar waveform in space and time including the local curvature-controlled dynein motor activity, [4,5] selective activation/deactivation of sliding microtubules due to transverse forces, [6] and regulation of dynein motor activity because of the sliding forces. [7] The resulting motion is 3D in nature, with the flagellar wave starting from the midpiece and traveling along a conical helix toward the end of the flagellum, causing the whole sperm body to counter-rotate. [8] Consequently, the flagellar waveform and sperm swimming path display helical, [5a,8a,c,9] twisted-planar, [8e] Sperm swim through the female reproductive tract by propagating a 3D flagellar wave that is self-regulatory in nature and driven by dynein motors. Traditional microscopy methods fail to capture the full dynamics of sperm flagellar activity as they only image and analyze sperm motility in 2D. Here, an automated platform to analyze sperm swimming behavior in 3D by using thinlens approximation and high-speed dark field microscopy to reconstruct the flagellar waveform in 3D is presented. It is found that head-tethered mouse sperm exhibit a rolling beating behavior in 3D with the beating frequency of 6.2 Hz using spectral analysis. The flagellar waveform bends in 3D, particularly in the distal regions, but is only weakly nonplanar and ambidextrous in nature, with the local helicity along the flagellum fluctuating between clockwise and counterclockwise handedness. These findings suggest a nonpersistent flagellar helicity. This method provides new opportunities for the accurate measurement of the full motion of eukaryotic flagella and cilia which is essential for a biophysical understanding of their activation by dynein motors.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smtd.202101089.

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Section: Resultsmentioning

confidence: 99%

Section: Flagellar Waveform Is Weakly Nonplanar and Ambidextrous In N...mentioning

confidence: 99%

Unraveling the Kinematics of Sperm Motion by Reconstructing the Flagellar Wave Motion in 3D

et al. 2022

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“…In this regard, recent results in CRISP2 knockout mice support the idea that ion channel regulation by CRISP proteins controls energy flows powering the axonema ( Nandagiri et al, 2021 ). Moreover, CRISP1, CRISP2, and CRISP4 have been proposed to be required to optimize sperm flagellum waveform ( Gaikwad et al, 2021 ).…”

Section: Evidence On the Relevance Of Crisp Proteins For Fertilization And Fertility Through The Use Of Knockout Modelsmentioning

confidence: 99%

Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility

Gonzalez

Sulzyk

Muñoz

et al. 2021

Front. Cell Dev. Biol.

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Mammalian fertilization is a complex process involving a series of successive sperm-egg interaction steps mediated by different molecules and mechanisms. Studies carried out during the past 30 years, using a group of proteins named CRISP (Cysteine-RIch Secretory Proteins), have significantly contributed to elucidating the molecular mechanisms underlying mammalian gamete interaction. The CRISP family is composed of four members (i.e., CRISP1-4) in mammals, mainly expressed in the male tract, present in spermatozoa and exhibiting Ca2+ channel regulatory abilities. Biochemical, molecular and genetic approaches show that each CRISP protein participates in more than one stage of gamete interaction (i.e., cumulus penetration, sperm-ZP binding, ZP penetration, gamete fusion) by either ligand-receptor interactions or the regulation of several capacitation-associated events (i.e., protein tyrosine phosphorylation, acrosome reaction, hyperactivation, etc.) likely through their ability to regulate different sperm ion channels. Moreover, deletion of different numbers and combination of Crisp genes leading to the generation of single, double, triple and quadruple knockout mice showed that CRISP proteins are essential for male fertility and are involved not only in gamete interaction but also in previous and subsequent steps such as sperm transport within the female tract and early embryo development. Collectively, these observations reveal that CRISP have evolved to perform redundant as well as specialized functions and are organized in functional modules within the family that work through independent pathways and contribute distinctly to fertility success. Redundancy and compensation mechanisms within protein families are particularly important for spermatozoa which are transcriptionally and translationally inactive cells carrying numerous protein families, emphasizing the importance of generating multiple knockout models to unmask the true functional relevance of family proteins. Considering the high sequence and functional homology between rodent and human CRISP proteins, these observations will contribute to a better understanding and diagnosis of human infertility as well as the development of new contraceptive options.

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Viscous Loading Regulates the Flagellar Energetics of Human and Bull Sperm

Yazdan Parast,

Veeraragavan,

Gaikwad

et al. 2023

Small Methods

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The viscoelastic properties of the female reproductive tract influence sperm swimming behavior, but the exact role of these rheological changes in regulating sperm energetics remains unknown. Using high‐speed dark‐field microscopy, the flagellar dynamics of free‐swimming sperm across a physiologically relevant range of viscosities is resolved. A transition from 3D to 2D slither swimming under an increased viscous loading is revealed, in the absence of any geometrical or chemical stimuli. This transition is species‐specific, aligning with viscosity variations within each species’ reproductive tract. Despite substantial drag increase, 2D slithering sperm maintain a steady swimming speed across a wide viscosity range (20–250 and 75–1000 mPa s for bull and human sperm) by dissipating over sixfold more energy into the fluid without elevating metabolic activity, potentially by altering the mechanisms of dynein motor activity. This energy‐efficient motility mode is ideally suited for the viscous environment of the female reproductive tract.

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CRISPs Function to Boost Sperm Power Output and Motility

Cited by 8 publications

References 55 publications

Unraveling the Kinematics of Sperm Motion by Reconstructing the Flagellar Wave Motion in 3D

Unraveling the Kinematics of Sperm Motion by Reconstructing the Flagellar Wave Motion in 3D

Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility

Viscous Loading Regulates the Flagellar Energetics of Human and Bull Sperm

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