Cutting edge: association of the motor protein nonmuscle myosin heavy chain-IIA with the C terminus of the chemokine receptor CXCR4 in T lymphocytes.
The binding of chemokines to their receptors guides lymphocyte migration. However, the precise mechanism that links the chemotactic signals with the energy and traction force generated by the actomyosin complex of the cell has not been elucidated. Using biochemical approaches and mass spectrometry analysis, we found an association between the C-termini of CXCR4 and CCR5 and the motor protein nonmuscle myosin H chain-IIA. Immunoprecipitation experiments revealed that this association also occurs between the endogenous molecules in T lymphocytes. As expected, myosin L chain was also associated with CXCR4. Confocal microscopy analysis showed that CXCR4 and motor protein nonmuscle myosin H chain-IIA colocalize at the leading edge of migrating T lymphocytes, together with filamentous actin and myosin L chain. These results provide the first evidence of a biochemical association between chemokine receptors and motor proteins, a mechanosignaling mechanism that may have a key role in lymphocyte migration.
Rey
Mercedes
M
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, c/Diego de León 62, E-28006 Madrid, Spain.
Vicente-Manzanares
Miguel
M
Viedma
Fernando
F
Yáñez-Mó
María
M
Urzainqui
Ana
A
Barreiro
Olga
O
Vázquez
Jesús
J
Sánchez-Madrid
Francisco
F
D000199:Actins / Q000378:metabolism / Q000502:physiology; D000595:Amino Acid Sequence; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D020409:Molecular Motor Proteins / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000378:metabolism* / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism* / Q000502:physiology; D019713:Receptors, CCR5 / Q000378:metabolism / Q000502:physiology; D019718:Receptors, CXCR4 / Q000378:metabolism* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D000199:Actins; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018994:Myosin Light Chains; D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D018995:Myosin Heavy Chains