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- W4297386569 abstract "Activation of the integrin phagocytic receptors CR3 (αMβ2, CD11b/CD18) and CR4 (αXβ2, CD11c/CD18) requires Rap1 activation and RIAM function. RIAM controls integrin activation by recruiting Talin to β2 subunits, enabling the Talin-Vinculin interaction, which in term bridges integrins to the actin-cytoskeleton. RIAM also recruits VASP to phagocytic cups and facilitates VASP phosphorylation and function promoting particle internalization. Using a CRISPR-Cas9 knockout approach, we have analyzed the requirement for RIAM, VASP and Vinculin expression in neutrophilic-HL-60 cells. All knockout cells displayed abolished phagocytosis that was accompanied by a significant and specific reduction in ITGAM (αM), ITGAX (αX) and ITGB2 (β2) mRNA, as revealed by RT-qPCR. RIAM, VASP and Vinculin KOs presented reduced cellular F-actin content that correlated with αM expression, as treatment with the actin filament polymerizing and stabilizing drug jasplakinolide, partially restored αM expression. In general, the expression of αX was less responsive to jasplakinolide treatment than αM, indicating that regulatory mechanisms independent of F-actin content may be involved. The Serum Response Factor (SRF) was investigated as the potential transcription factor controlling αMβ2 expression, since its coactivator MRTF-A requires actin polymerization to induce transcription. Immunofluorescent MRTF-A localization in parental cells was primarily nuclear, while in knockouts it exhibited a diffuse cytoplasmic pattern. Localization of FHL-2 (SRF corepressor) was mainly sub-membranous in parental HL-60 cells, but in knockouts the localization was disperse in the cytoplasm and the nucleus, suggesting RIAM, VASP and Vinculin are required to maintain FHL-2 close to cytoplasmic membranes, reducing its nuclear localization and inhibiting its corepressor activity. Finally, reexpression of VASP in the VASP knockout resulted in a complete reversion of the phenotype, as knock-ins restored αM expression. Taken together, our results suggest that RIAM, VASP and Vinculin, are necessary for the correct expression of αMβ2 and αXβ2 during neutrophilic differentiation in the human promyelocytic HL-60 cell line, and strongly point to an involvement of these proteins in the acquisition of a phagocytic phenotype." @default.
- W4297386569 created "2022-09-28" @default.
- W4297386569 creator A5000671033 @default.
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- W4297386569 date "2022-09-27" @default.
- W4297386569 modified "2023-10-18" @default.
- W4297386569 title "Expression of the phagocytic receptors αMβ2 and αXβ2 is controlled by RIAM, VASP and Vinculin in neutrophil-differentiated HL-60 cells" @default.
- W4297386569 cites W1262336387 @default.
- W4297386569 cites W1496174628 @default.
- W4297386569 cites W1548000107 @default.
- W4297386569 cites W1576773659 @default.
- W4297386569 cites W1586082383 @default.
- W4297386569 cites W1599437019 @default.
- W4297386569 cites W1745881199 @default.
- W4297386569 cites W1947723185 @default.
- W4297386569 cites W1976389026 @default.
- W4297386569 cites W1984490937 @default.
- W4297386569 cites W1994964776 @default.
- W4297386569 cites W1998539678 @default.
- W4297386569 cites W1999663047 @default.
- W4297386569 cites W2002596571 @default.
- W4297386569 cites W2003140132 @default.
- W4297386569 cites W2003698382 @default.
- W4297386569 cites W2005663928 @default.
- W4297386569 cites W2006010692 @default.
- W4297386569 cites W2007705388 @default.
- W4297386569 cites W2019985975 @default.
- W4297386569 cites W2024718387 @default.
- W4297386569 cites W2024814259 @default.
- W4297386569 cites W2025107609 @default.
- W4297386569 cites W2025559292 @default.
- W4297386569 cites W2027266132 @default.
- W4297386569 cites W2030443017 @default.
- W4297386569 cites W2032335449 @default.
- W4297386569 cites W2036176224 @default.
- W4297386569 cites W2036882237 @default.
- W4297386569 cites W2039487041 @default.
- W4297386569 cites W2039502415 @default.
- W4297386569 cites W2041343947 @default.
- W4297386569 cites W2059716736 @default.
- W4297386569 cites W2067723708 @default.
- W4297386569 cites W2072913808 @default.
- W4297386569 cites W2077702220 @default.
- W4297386569 cites W2077954297 @default.
- W4297386569 cites W2079281248 @default.
- W4297386569 cites W2080249478 @default.
- W4297386569 cites W2080676934 @default.
- W4297386569 cites W2081438791 @default.
- W4297386569 cites W2085776541 @default.
- W4297386569 cites W2086608191 @default.
- W4297386569 cites W2087275528 @default.
- W4297386569 cites W2092845229 @default.
- W4297386569 cites W2097025955 @default.
- W4297386569 cites W2102206149 @default.
- W4297386569 cites W2107277218 @default.
- W4297386569 cites W2108770100 @default.
- W4297386569 cites W2111939342 @default.
- W4297386569 cites W2116312858 @default.
- W4297386569 cites W2123182436 @default.
- W4297386569 cites W2131932355 @default.
- W4297386569 cites W2141089307 @default.
- W4297386569 cites W2144518949 @default.
- W4297386569 cites W2145676008 @default.
- W4297386569 cites W2146756090 @default.
- W4297386569 cites W2149436537 @default.
- W4297386569 cites W2154415816 @default.
- W4297386569 cites W2159641065 @default.
- W4297386569 cites W2168539398 @default.
- W4297386569 cites W2168683563 @default.
- W4297386569 cites W2192080449 @default.
- W4297386569 cites W2272040821 @default.
- W4297386569 cites W2531812293 @default.
- W4297386569 cites W2588121804 @default.
- W4297386569 cites W2603933042 @default.
- W4297386569 cites W2604830165 @default.
- W4297386569 cites W2735067167 @default.
- W4297386569 cites W2750137696 @default.
- W4297386569 cites W2784865851 @default.
- W4297386569 cites W2790136196 @default.
- W4297386569 cites W2807783331 @default.
- W4297386569 cites W2901644785 @default.
- W4297386569 cites W2912250672 @default.
- W4297386569 cites W2915419329 @default.
- W4297386569 cites W2947069836 @default.
- W4297386569 cites W2965497077 @default.
- W4297386569 cites W2981462453 @default.
- W4297386569 cites W2999681619 @default.
- W4297386569 cites W3004805262 @default.
- W4297386569 cites W3016126718 @default.
- W4297386569 cites W3022104547 @default.
- W4297386569 cites W3023929055 @default.
- W4297386569 cites W3036024147 @default.
- W4297386569 cites W3036823689 @default.