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Fluxes of energy generate active forces in living matter, yet also active fluctuations. As a canonical example, collections of molecular motors exhibit spontaneous oscillations with frequency jitter caused by nonequilibrium phase fluctuations. We investigate phase fluctuations in reactivated axonemes, which are accessible to direct manipulation. We quantify the precision of axonemal oscillations after controlled chemical removal of dynein motors, providing an experimental test for the theory prediction that the quality factor of motor oscillations should increase with motor number. Our quantification reveals specialized roles of inner and outer arm dynein motors. This supports a model in which inner dyneins serve as master pace-makers, to which outer arm dyneins become entrained, consistent with recent insight provided by structural biology.
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http://dx.doi.org/10.1073/pnas.2406244121 | DOI Listing |
J Cell Sci
September 2025
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
The microtubule motor dynein-2 is responsible for retrograde intraflagellar transport (IFT), a process critical for cilia assembly and cilium-dependent signaling. Mutations in genes encoding dynein-2 subunits interfere with ciliogenesis and are among the most frequent causes of skeletal ciliopathies. Despite its importance, little is known regarding dynein-2 assembly and regulation.
View Article and Find Full Text PDFCurr Biol
September 2025
Department of Molecular and Cellular Biology, University of California, 1 Shields Avenue, Davis, CA 95616, USA. Electronic address:
Nuclear migration plays a fundamental role in development, requiring precise spatiotemporal control of bidirectional movement through dynein and kinesin motors. Here, we uncover a differential isoform-dependent mechanism for developmental regulation of nuclear migration directionality. The nuclear envelope Klarsicht/ANC-1/Syne homology (KASH) protein UNC-83 in Caenorhabditis elegans exists in multiple isoforms that differentially control motor activity to achieve tissue-specific nuclear positioning.
View Article and Find Full Text PDFFEBS J
August 2025
Department of Biotechnology and Life Sciences, Centre of NeuroScience, University of Insubria, Busto Arsizio, Italy.
Cyclin-dependent kinase-like 5 (CDKL5) is a serine-threonine kinase implicated in regulating microtubule (MT) dynamics. Mutations in CDKL5 are associated with a rare neurodevelopmental disease called CDKL5 deficiency disorder (CDD), which is characterized by early-onset seizures and intellectual disabilities. Microtubule (MT)-related functions of CDKL5 are in part correlated with its interaction with MT-associated proteins, such as CAP-Gly domain-containing linker protein 1 [CLIP1; also known as cytoplasmic linker protein 170 alpha-2 (CLIP170)].
View Article and Find Full Text PDFThe fusion of newly formed early endosomal vesicles after endocytosis is a crucial step in viral infection. It facilitates the transition of many viruses from viral internalization to downstream intracellular trafficking within the endosomal network, ultimately enabling their delivery to intracellular replication sites. Despite its significance, the molecular mechanisms regulating the fusion of these vesicles remain poorly understood.
View Article and Find Full Text PDFCytoskeleton (Hoboken)
August 2025
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA.
Dyneins were present in the last eukaryotic common ancestor (LECA) and play key roles in eukaryotic biology. Axonemal dyneins form the inner and outer arms that power ciliary beating, and it has long been recognized that outer arms in some organisms contain two different heavy chain motors, whereas those from other species contain a third unit that imparts enhanced motive force during ciliary beating. Previous phylogenetic analyses suggested that this third motor derived from a gene duplication event in the LECA, followed by the subsequent replacement of the N-terminal assembly domain with one formed from kelch and immunoglobulin repeats.
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