BCL6 suppresses RhoA activity to alter macrophage morphology and motility

Fiona Pixley, Y. Xiong, R.Y. Yu, E.A. Sahai, E.R. Stanley, B.H. Ye

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37 Citations (Scopus)

Abstract

BCL6 is a potent transcriptional repressor that plays important roles in germinal center formation, T helper cell differentiation and lymphomagenesis and regulates expression of several chemokine genes in macrophages. In a further investigation of its role in macrophages, we show that BCL6 inactivation in primary bone marrow-derived macrophages leads to decreased polarization, motility and cell spreading accompanied by an increase in peripheral focal complexes, anchored F-actin bundles and cortical F-actin density. These changes were associated with excess RhoA activation. C3 transferase inhibition of RhoA activity reverted the adhesion structure phenotype, which was not affected by Rho kinase inhibitors, suggesting that other downstream effectors of Rho maintain this Bcl6(-/-) phenotype. Excess RhoA activation in BCL6-deficient macrophages is associated with a decrease in the p120RasGAP (RASA1)-mediated translocation of p190RhoGAP (GRLF1) to active RhoA at the plasma membrane and a reduction in cell surface expression of the CSF1R that has been reported to recruit RasGAP to the plasma membrane. Reconstitution of BCL6 expression in Bcl6(-/-) macrophages results in complete reversion of the morphological phenotype and a significant increase in cell surface CSF1R expression whereas overexpression of the CSF1R corrects the polarization and adhesion structure defects. These results demonstrate that BCL6 suppresses RhoA activity, largely through upregulation of surface CSF1R expression, to modulate cytoskeletal and adhesion structures and increase the motility of macrophages.
Original languageEnglish
Pages (from-to)1873-1883
JournalJournal of Cell Science
Volume118
Issue number9
DOIs
Publication statusPublished - 2005

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    Pixley, F., Xiong, Y., Yu, R. Y., Sahai, E. A., Stanley, E. R., & Ye, B. H. (2005). BCL6 suppresses RhoA activity to alter macrophage morphology and motility. Journal of Cell Science, 118(9), 1873-1883. https://doi.org/10.1242/jcs.02314