期刊
SCIENCE SIGNALING
卷 7, 期 322, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.2004872
关键词
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资金
- Spanish Ministerio de Economia y Competitividad (MINECO) [SAF2011-25834, SAF2010-16044]
- Comunidad de Madrid [INDISNET-S2011/BMD-2332]
- Instituto de Salud Carlos III (ISCIII) [RD12/0042/0028, RD12/0042/0056, CP11/00145]
- Progeria Research Foundation [PRF 2012-42]
- European Commission [ERC-2011AdG 294340-GENTRIS, 317916-Liphos]
- Sara Borrell ISCIII program [CP11/00145]
- Miguel Servet ISCIII program [CP11/00145]
- Fundacion Mario Losantos del Campo
- Fundacion Ferrer para la Investigacion
- Obra Social Cajastur
- Spanish MINECO
- Pro-CNIC Foundation
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.
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