The intracellular domain of CD44 promotes the fusion of macrophages.
Macrophages seed all tissues in which they have the ability, in specific and rare instances, to fuse with themselves and to differentiate into osteoclasts in bone or into giant cells in chronic inflammatory reactions. Although these cells play a central role in osteoporosis and in foreign body rejection, respectively, the molecular mechanism used by macrophages to fuse remains poorly understood. Macrophages might also fuse with somatic and tumor cells to promote tissue repair and metastasis, respectively. We reported that CD44 expression is highly induced in macrophages at the onset of fusion in which it plays a role. We report now that the intracellular domain of CD44 (CD44ICD) is cleaved in macrophages undergoing fusion and that presenilin inhibitors prevent the release of CD44ICD and fusion. We also show that CD44ICD promotes the fusion of tissue macrophages and bone marrow-derived macrophages. Finally, we report that CD44ICD is localized in the nucleus of macrophages in which it promotes the activation of NF-kappaB. These observations open avenues to study the role of CD44ICD in blood cells and tumors.
Cui
Weiguo
W
Yale University School of Medicine, Department of Orthopaedics and Rehabilitation, 333 Cedar St, New Haven, CT 06510, USA.
Ke
Juan Zhang
JZ
Zhang
Qing
Q
Ke
Hua-Zhu
HZ
Chalouni
Cécile
C
Vignery
Agnès
A
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002459:Cell Fusion; D002467:Cell Nucleus / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053764:Presenilin-1; D017434:Protein Structure, Tertiary; D053245:RANK Ligand; D051381:Rats; D011916:Rats, Inbred F344; D053246:Receptor Activator of Nuclear Factor-kappa B; D012190:Retroviridae / Q000235:genetics; D013347:Subcellular Fractions
D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D016328:NF-kappa B; D053764:Presenilin-1; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D008156:Luciferases