{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T02:54:11Z","timestamp":1773024851846,"version":"3.50.1"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Activation of the integrin phagocytic receptors CR3 (\u03b1<jats:sub>M<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub>, CD11b\/CD18) and CR4 (\u03b1<jats:sub>X<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub>, CD11c\/CD18) requires Rap1 activation and RIAM function. RIAM controls integrin activation by recruiting Talin to \u03b2<jats:sub>2<\/jats:sub>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 (\u03b1<jats:sub>M<\/jats:sub>), ITGAX (\u03b1<jats:sub>X<\/jats:sub>) and ITGB2 (\u03b2<jats:sub>2<\/jats:sub>) mRNA, as revealed by RT-qPCR. RIAM, VASP and Vinculin KOs presented reduced cellular F-actin content that correlated with \u03b1M expression, as treatment with the actin filament polymerizing and stabilizing drug jasplakinolide, partially restored \u03b1<jats:sub>M<\/jats:sub>expression. In general, the expression of \u03b1<jats:sub>X<\/jats:sub>was less responsive to jasplakinolide treatment than \u03b1<jats:sub>M<\/jats:sub>, 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 \u03b1<jats:sub>M<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub>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 \u03b1<jats:sub>M<\/jats:sub>expression. Taken together, our results suggest that RIAM, VASP and Vinculin, are necessary for the correct expression of \u03b1<jats:sub>M<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub>and \u03b1<jats:sub>X<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub>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.<\/jats:p>","DOI":"10.3389\/fimmu.2022.951280","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T16:25:47Z","timestamp":1664295947000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Expression of the phagocytic receptors \u03b1M\u03b22 and \u03b1X\u03b22 is controlled by RIAM, VASP and Vinculin in neutrophil-differentiated HL-60 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