Actin polymerization-dependent activation of Cas-L promotes immunological synapse stability.
Immunol Cell Biol
; 94(10): 981-993, 2016 11.
Article
in En
| MEDLINE
| ID: mdl-27359298
ABSTRACT
The immunological synapse formed between a T-cell and an antigen-presenting cell is important for cell-cell communication during T-cell-mediated immune responses. Immunological synapse formation begins with stimulation of the T-cell receptor (TCR). TCR microclusters are assembled and transported to the center of the immunological synapse in an actin polymerization-dependent process. However, the physical link between TCR and actin remains elusive. Here we show that lymphocyte-specific Crk-associated substrate (Cas-L), a member of a force sensing protein family, is required for transport of TCR microclusters and for establishing synapse stability. We found that Cas-L is phosphorylated at TCR microclusters in an actin polymerization-dependent fashion. Furthermore, Cas-L participates in a positive feedback loop leading to amplification of Ca2+ signaling, inside-out integrin activation, and actomyosin contraction. We propose a new role for Cas-L in T-cell activation as a mechanical transducer linking TCR microclusters to the underlying actin network and coordinating multiple actin-dependent structures in the immunological synapse. Our studies highlight the importance of mechanotransduction processes in T-cell-mediated immune responses.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Actins
/
Crk-Associated Substrate Protein
/
Immunological Synapses
/
Polymerization
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Immunol Cell Biol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2016
Document type:
Article