| First Author | González-Granado JM | Year | 2014 |
| Journal | Sci Signal | Volume | 7 |
| Issue | 322 | Pages | ra37 |
| PubMed ID | 24757177 | Mgi Jnum | J:259044 |
| Mgi Id | MGI:6140512 | Doi | 10.1126/scisignal.2004872 |
| Citation | Gonzalez-Granado JM, et al. (2014) Nuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activation. Sci Signal 7(322):ra37 |
| abstractText | In many cell types, nuclear A-type lamins regulate multiple cellular functions, including higher-order genome organization, DNA replication and repair, gene transcription, and signal transduction; however, their role in specialized immune cells remains largely unexplored. We showed that the abundance of A-type lamins was almost negligible in resting naive T lymphocytes, but was increased upon activation of the T cell receptor (TCR). The increase in lamin-A was an early event that accelerated formation of the immunological synapse between T cells and antigen-presenting cells. Polymerization of F-actin in T cells is a critical step for immunological synapse formation, and lamin-A interacted with the linker of nucleoskeleton and cytoskeleton (LINC) complex to promote F-actin polymerization. We also showed that lamin-A expression accelerated TCR clustering and led to enhanced downstream signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, as well as increased target gene expression. Pharmacological inhibition of the ERK pathway reduced lamin-A-dependent T cell activation. Moreover, mice lacking lamin-A in immune cells exhibited impaired T cell responses in vivo. These findings underscore the importance of A-type lamins for TCR activation and identify lamin-A as a previously unappreciated regulator of the immune response. |
