EBV attachment stimulates FHOS/FHOD1 redistribution and co-aggregation with CD21: formin interactions with the cytoplasmic domain of human CD21.
CD21 is a multifunctional receptor for Epstein-Barr virus (EBV), for C3dg and for CD23. Upon engagement of immune complexes CD21 modulates immunoreceptor signaling, linking innate and adaptive immune responses. The mechanisms enabling CD21 to independently relay information between the exterior and interior of the cell, however, remain unresolved. We show that formin homologue overexpressed in spleen (FHOS/FHOD1) binds the cytoplasmic domain of human CD21 through its C terminus. When expressed in cells, EGFP-FHOS localizes to the cytoplasm and accumulates with actin in membrane protrusions. Plasma membrane aggregation, redistribution and co-localization of both proteins are stimulated when EBV (ligand) binds CD21. Though widely expressed, FHOS RNA is most abundant in the littoral cell, a major constituent of the red pulp of human spleen believed to function in antigen filtration. Formins are molecular scaffolds that nucleate actin by a pathway distinct from Arp2/3 complex, linking signal transduction to actin reorganization and gene transcription. Thus, ligand stimulation of FHOS-CD21 interaction may transmit signals through promotion of cytoskeletal rearrangement. Moreover, formin recruitment to sites of actin assembly initiated by immunoreceptors could be a general mechanism whereby co-receptors such as CD21 modulate intracellular signaling.
Gill
Michael B
MB
Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Roecklein-Canfield
Jennifer
J
Sage
David R
DR
Zambela-Soediono
Maria
M
Longtine
Nina
N
Uknis
Marc
M
Fingeroth
Joyce D
JD
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D000080865:Formins; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017464:Receptors, Complement 3d / Q000737:chemistry* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D020798:Two-Hybrid System Techniques
C120021:FHOD1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D009687:Nuclear Proteins; D017464:Receptors, Complement 3d; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins