Cytokinesis requires the coordination of cytoskeletal and plasma membrane dynamics. A role for phosphatidylinositol lipids has been proposed for the successful completion of cytokinesis but this is still poorly characterised. Here, we show mutants of the gene vibrator, previously found to encode the Drosophila phosphatidylinositol transfer protein, produce multinucleate cells indicative of cytokinesis failure in male meiosis. Examination of fixed preparations of mutant spermatocytes showed contractile rings of anillin and actin that were of normal appearance at early stages but were larger and less well organised at later stages of cytokinesis than in wild-type cells. Time-lapse imaging revealed sequential defects in cytokinesis of vibrator spermatocytes. In cells that fail cytokinesis, central spindle formation occurred correctly, but furrow ingression was delayed and the central spindle did not become compressed to the extent seen in wild-type cells. Cells then stalled at this point before the apparent connection between the constricted cytoskeleton and the plasma membrane was lost; the furrow then underwent elastic regression. We discuss these defects in relation to multiple functions of phosphoinositol lipids in regulating actin dynamics and membrane synthesis.
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Int J Mol Sci
October 2024
Department of Biomedical Sciences, University of South Alabama, Mobile, AL 36688-0002, USA.
Various dietary supplements have been shown to extend the life span of , including several that promote autophagy, such as rapamycin and spermidine. The goal of the study presented here was to test numerous additional potential anti-aging supplements, primarily inhibitors of the target of rapamycin (TOR) and/or phosphatidylinositol 3-kinase (PI3K). Using a single, comparatively long-lived test strain, screening was performed in male flies supplemented either throughout adulthood or, in a few cases, beginning in middle or late adult life, with concentrations spanning 4-6 orders of magnitude in most cases.
View Article and Find Full Text PDFPLoS One
October 2024
Department of Oncological Sciences, Salt Lake City, Utah, United States of America.
Rabex-5 (also called RabGEF1), a protein originally characterized for its Rab5 GEF function, also has an A20-like E3 ubiquitin ligase domain. We and others reported that Rabex-5 E3 activity promotes Ras mono- and di-ubiquitination to inhibit Ras signaling in Drosophila and mammals. Subsequently, we reported that Rabex-5 inhibits Notch signaling in the Drosophila hematopoietic system.
View Article and Find Full Text PDFBiochemistry
November 2024
Department of Biology, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune 411008, Maharashtra, India.
The chemoproteomics technique, activity-based protein profiling (ABPP), has proven to be an invaluable tool in assigning functions to enzymes. The serine hydrolase (SH) enzyme superfamily, in particular, has served as an excellent example in displaying the versatility of various ABPP platforms and has resulted in a comprehensive cataloging of the biochemical activities associated within this superfamily. Besides SHs, in mammals, several other enzyme classes have been thoroughly investigated using ABPP platforms.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2024
Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.
Eur J Neurosci
October 2024
Department of Biomedical Sciences, University of Windsor, Windsor, Ontario, Canada.
Phosphoinositides, such as PI(4,5)P, are known to function as structural components of membranes, signalling molecules, markers of membrane identity, mediators of protein recruitment and regulators of neurotransmission and synaptic development. Phosphatidylinositol 4-kinases (PI4Ks) synthesize PI4P, which are precursors for PI(4,5)P, but may also have independent functions. The roles of PI4Ks in neurotransmission and synaptic development have not been studied in detail.
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