Format

Send to

Choose Destination
See comment in PubMed Commons below
Sci Signal. 2014 Apr 22;7(322):ra37. doi: 10.1126/scisignal.2004872.

Nuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activation.

Author information

1
Department of Epidemiology, Atherothrombosis and Imaging, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
2
Vascular Biology and Inflammation. CNIC, Madrid, Spain.
3
Servicio de Inmunología, Hospital de la Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
4
Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo-IUOPA, Oviedo, Spain.
#
Contributed equally

Abstract

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 naïve 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.

Comment in

PMID:
24757177
PMCID:
PMC4337980
DOI:
10.1126/scisignal.2004872
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center