Jak3 enables chemokine-dependent actin cytoskeleton reorganization by regulating cofilin and Rac/Rhoa GTPases activation
Por:
Ambriz-Peña X., García-Zepeda E.A., Meza I., Soldevila G.
Publicada:
3 feb 2014
Resumen:
We have previously shown that Jak3 is involved in the signaling pathways of CCR7, CCR9 and CXCR4 in murine T lymphocytes and that Jak3-/- lymphocytes display an intrinsic defect in homing to peripheral lymph nodes. However, the molecular mechanism underlying the defective migration observed in Jak3-/- lymphocytes remains elusive. Here, it is demonstrated for the first time, that Jak3 is required for the actin cytoskeleton reorganization in T lymphocytes responding to chemokines. It was found that Jak3 regulates actin polymerization by controlling cofilin inactivation in response to CCL21 and CXCL12. Interestingly, cofilin inactivation was not precluded in PTX- treated cells despite their impaired actin polymerization. Additionally, Jak3 was required for small GTPases Rac1 and RhoA activation, which are indispensable for acquisition of the migratory cell phenotype and the generation of a functional leading edge and uropod, respectively. This defect correlates with data obtained by time-lapse video-microscopy showing an incompetent uropod formation and impaired motility in Jak3-pharmacologically inhibited T lymphocytes. Our data support a new model in which Jak3 and heterotrimeric G proteins can use independent, but complementary, signaling pathways to regulate actin cytoskeleton dynamics during cell migration in response to chemokines. © 2014 Ambriz-Peña et al.
Filiaciones:
Ambriz-Peña X.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Mexico City 04510, DF, Mexico
García-Zepeda E.A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Mexico City 04510, DF, Mexico
Meza I.:
Departamento de Biomedicina Molecular, Centro de Investigación Y de Estudios Avanzados (CINVESTAV IPN), México, Distrito Federal, Mexico
Soldevila G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Inmunol, Mexico City 04510, DF, Mexico
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