Unc104/KIF1A belongs to a class of monomeric kinesin motors that have been thought to possess an unusual motility mechanism. Unlike the unidirectional motion driven by the coordinated actions of the two heads in conventional kinesins, single-headed KIF1A was reported to undergo biased diffusional motion along microtubules. Here, we show that Unc104/KIF1A can dimerize and move unidirectionally and processively with rapid velocities characteristic of transport in living cells. These results suggest that Unc104/KIF1A operates in vivo by a mechanism similar to conventional kinesin and that regulation of motor dimerization may be used to control transport by this class of kinesins.
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http://dx.doi.org/10.1126/science.1073386 | DOI Listing |
BMC Neurosci
January 2025
Department of Operative Dentistry and Periodontology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration of midbrain dopaminergic neurons (mDANs) and nigrostriatal projections results in severe motor symptoms. While the preferential loss of mDANs has not been fully understood yet, the cell type-specific vulnerability has been linked to a unique intracellular milieu, influenced by dopamine metabolism, high demand for mitochondrial activity, and increased level of oxidative stress (OS).
View Article and Find Full Text PDFEur J Trauma Emerg Surg
January 2025
Department of Emergency Medicine, Teikyo University of Medicine, 2- 11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan.
Purpose: D-dimer, a fibrinolysis indicator, may predict functional and life outcomes in traumatic brain injury (TBI) patients. We aimed to identify optimal D-dimer cutoff values for poor functional outcomes in severe TBI.
Methods: We used data from a multi-centre prospective observational cohort study that included patients with TBI with a Glasgow Coma Scale (GCS) score ≤ 8 within 48 h after injury or required neurosurgical procedures.
Environ Sci Technol
January 2025
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu Province 210023, China.
Nanoplastics (NPs) are ubiquitous in the environment, posing significant threats to biological systems, including nervous systems, across various trophic levels. Nevertheless, the molecular mechanisms behind the size-dependent neurotoxicity of NPs remain unclear. Here, we investigated the neurotoxicity of 20 and 100 nm polystyrene NPs (PS-NPs) to zebrafish.
View Article and Find Full Text PDFCytoplasmic 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 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.
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