Intracellular and nuclear CXCR4 signaling promotes terminal erythroblast differentiation and enucleation
Year: 2025
Type: article
Abstract: The chemokine CXCL12 signals through its receptor CXCR4 to induce the migration of all leukocyte types and multiple other cell types. Here, we report that CXCR4 is expressed in mouse erythroblasts, the bone marrow erythroid precursors, in which it stimulates erythrocyte generation instead of chemotaxis. CXCR4 signaling promoted homeostatic erythroblast maturation and increased the expression of genes mainly involved in metabolism and chromatin organization. Consequently, genetic depletion of CXCR4 in erythroblasts inhibited late erythropoiesis and diminished bone marrow erythroid outputs. Binding of CXCL12 to CXCR4 stimulated its rapid endocytosis and translocation together with Gα i or phosphorylated β-arrestin1 into distinct intracellular compartments, including the nuclear envelope and nucleus. CXCL12 signaling promoted erythroblast elongation and the condensation and excentric positioning of nuclei and stimulated rapid perinuclear Ca 2+ transients that immediately preceded erythroblast enucleation. These findings highlight previously uncharacterized physiological roles for CXCR4 and bone marrow–derived CXCL12 in erythropoiesis.
Source: Science Signaling
Institutions: Queen Mary University of London, University of Konstanz, Institute of Cell Biology and Immunology Thurgau, William Harvey Research Institute, Medical University of Graz, University of Bern, MRC Laboratory for Molecular Cell Biology, University College London, Ludwig-Maximilians-Universität München
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4411374107