We demonstrate a technique for investigating the energetics of flagella or cilia. We record the planar beating of tethered mouse sperm at high resolution. Beating waveforms are reconstructed using proper orthogonal decomposition of the centerline tangent-angle profiles. Energy conservation is employed to obtain the mechanical power exerted by the dynein motors from the observed kinematics. A large proportion of the mechanical power exerted by the dynein motors is dissipated internally by the motors themselves. There could also be significant dissipation within the passive structures of the flagellum. The total internal dissipation is considerably greater than the hydrodynamic dissipation in the aqueous medium outside. The net power input from the dynein motors in sperm from -knockout mice is significantly smaller than in wildtype samples, indicating that ion-channel regulation by cysteine-rich secretory proteins controls energy flows powering the axoneme.
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http://dx.doi.org/10.7554/eLife.62524 | DOI Listing |
Dynein-1 is a microtubule motor responsible for the transport of cytoplasmic cargoes. Activation of motility requires it first overcome an autoinhibited state prior to its assembly with dynactin and a cargo adaptor. Studies suggest that Lis1 may relieve dynein's autoinhibited state.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06511, USA.
Cytoplasmic dynein-1 (dynein) is the primary motor for the retrograde transport of intracellular cargoes along microtubules. The activation of the dynein transport machinery requires the opening of its autoinhibited Phi conformation by Lis1 and Nde1/Ndel1, but the underlying mechanism remains unclear. Using biochemical reconstitution and cryo-electron microscopy, we show that Nde1 significantly enhances Lis1 binding to autoinhibited dynein and facilitates the opening of Phi.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06511, USA.
Cytoplasmic dynein-1, a microtubule-based motor protein, requires dynactin and an adaptor to form the processive dynein-dynactin-adaptor (DDA) complex. The role of microtubules in DDA assembly has been elusive. Here, we reveal detailed structural insights into microtubule-mediated DDA assembly using cryo-electron microscopy.
View Article and Find Full Text PDFCytoskeleton (Hoboken)
January 2025
Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka, Japan.
Dyneins are huge motor protein complexes that are essential for cell motility, cell division, and intracellular transport. Dyneins are classified into three major subfamilies, namely cytoplasmic, intraflagellar-transport (IFT), and ciliary dyneins, based on their intracellular localization and functions. Recently, several near-atomic resolution structures have been reported for cytoplasmic/IFT dyneins.
View Article and Find Full Text PDFAndrology
January 2025
Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, Team "Physiopathology and Pathophysiology of Sperm Cells", Grenoble, France.
Background: In mammals, sperm fertilization potential relies on efficient progression within the female genital tract to reach and fertilize the oocyte. This fundamental property is supported by the flagellum, an evolutionarily conserved organelle, which contains dynein motor proteins that provide the mechanical force for sperm propulsion and motility. Primary motility of the sperm cells is acquired during their transit through the epididymis and hyperactivated motility is acquired throughout the journey in the female genital tract by a process called capacitation.
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