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METTL3-mediated CEP170 m6A modifications in spindle orientation and esophageal cancer cell proliferation.
Int Immunopharmacol
December 2024
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China. Electronic address:
Esophageal cancer is a major malignancy with a high incidence and poor prognosis. To elucidate the mechanisms underlying its progression, particularly with respect to cell division and spindle orientation, we investigated the role of m6A modifications and the centrosomal protein CEP170. Using m6A-seq and RNA-seq of esophageal cancer tissues and adjacent normal tissues, we identified significant alterations in m6A modifications and gene expression, highlighting the upregulation and m6A enrichment of CEP170 in tumor tissues.
View Article and Find Full Text PDFDNA tensiometer reveals catch-bond detachment kinetics of kinesin-1, -2 and -3.
bioRxiv
December 2024
Department of Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania, USA.
Bidirectional cargo transport by kinesin and dynein is essential for cell viability and defects are linked to neurodegenerative diseases. The competition between motors is described as a tug-of-war, and computational modeling suggests that the load-dependent off-rate is the strongest determinant of which motor 'wins'. Optical tweezer experiments find that the load-dependent detachment sensitivity of transport kinesins is kinesin-3 > kinesin-2 > kinesin-1.
View Article and Find Full Text PDFLAMTOR1 regulates dendritic lysosomal positioning in hippocampal neurons through TRPML1 inhibition.
Front Cell Neurosci
November 2024
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United States.
Intracellular lysosomal trafficking and positioning are fundamental cellular processes critical for proper neuronal function. Among the diverse array of proteins involved in regulating lysosomal positioning, the Transient Receptor Potential Mucolipin 1 (TRPML1) and the Ragulator complex have emerged as central players. TRPML1, a lysosomal cation channel, has been implicated in lysosomal biogenesis, endosomal/lysosomal trafficking including in neuronal dendrites, and autophagy.
View Article and Find Full Text PDFNovel bi-allelic DNAH3 variants cause oligoasthenoteratozoospermia.
Front Endocrinol (Lausanne)
November 2024
Department of Andrology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Background: Oligoasthenoteratozoospermia (OAT) is a widespread cause of male infertility. One of the usual clinical manifestations of OAT is multiple morphological abnormalities of the sperm flagella (MMAF), which are frequently associated with mutations and defects in the dynein family. However, the relationship between the newly identified Dynein Axonemal Heavy Chain 3 (DNAH3) mutation and oligonasthenospermia in humans has not yet been established.
View Article and Find Full Text PDFUnraveling the interplay of kinesin-1, tau, and microtubules in neurodegeneration associated with Alzheimer's disease.
Front Cell Neurosci
October 2024
Li Ka Shing Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Alzheimer's disease (AD) is marked by the gradual and age-related deterioration of nerve cells in the central nervous system. The histopathological features observed in the brain affected by AD are the aberrant buildup of extracellular and intracellular amyloid-β and the formation of neurofibrillary tangles consisting of hyperphosphorylated tau protein. Axonal transport is a fundamental process for cargo movement along axons and relies on molecular motors like kinesins and dyneins.
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