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- W2897070568 abstract "Actin cytoskeleton assembly occurs at phosphoinositide-rich membranes in cells, and controls membrane shape, intracellular vesicle transport, and cargo sorting. OCRL encodes a phosphoinositide 5-phosphatase that regulates the composition of diverse cellular membranes, and thus modulates actin assembly during many cellular processes, including endocytosis, autophagosome-lysosome fusion, cytokinesis, and endosomal trafficking. Mutations in OCRL cause Lowe Syndrome in humans, and excess actin assembly has been observed in patient cells and has been suggested as a therapeutic target. However, we still do not know whether and how this aberrant actin assembly contributes to disease symptoms. Mutations in the Drosophila melanogaster OCRL homolog, docrl, exhibit a similar accumulation of PI(4,5)P2 and actin filaments, along with broad endocytic and membrane trafficking dysfunction in cells of the innate immune system, ultimately leading to pathological immune cell activation. We previously found that trafficking defects and immune cell activation in docrl mutants derive from defects in late and recycling endosome traffic, and I hypothesized that aberrant actin filament assembly on these compartments may drive the dysfunction observed in docrl mutants. I found that in docrl mutant cells, actin filaments are strongly enriched on Rab7- and Rab11-positive endosomes, and moderately enriched on Rab5-positive endosomes. Further, I found that this aberrant actin filament assembly correlated with abnormal Arp3 recruitment to endosomes and is dependent on JNK signaling. However, suppressing actin filament accumulation did not reverse immune cell activation. These findings expand our understanding of endosomal trafficking disruption and suggest that intracellular aberrant actin filament assembly may lead to some, but not all, of the defects observed in Lowe Syndrome." @default.
- W2897070568 created "2018-10-26" @default.
- W2897070568 creator A5065832387 @default.
- W2897070568 date "2017-01-01" @default.
- W2897070568 modified "2023-09-26" @default.
- W2897070568 title "Analysis of the role of actin filament assembly in endosomal and immune dysfunction in docrl mutants" @default.
- W2897070568 hasPublicationYear "2017" @default.
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