RT Journal Article
SR Electronic
T1 Cytoskeletal tension actively sustains the migratory T cell synaptic contact
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 437236
DO 10.1101/437236
A1 Sudha Kumari
A1 Michael Mak
A1 Yehchuin Poh
A1 Mira Tohme
A1 Nicki Watson
A1 Mariane Melo
A1 Erin Janssen
A1 Michael Dustin
A1 Raif Geha
A1 Darrell J. Irvine
YR 2019
UL http://biorxiv.org/content/early/2019/05/04/437236.abstract
AB When migratory T cells encounter antigen presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T cell immunity. While the cellular processes underlying synapse formation have been well-characterized, those that maintain the symmetry, and thereby the stability of the synapse remain unknown. Here we identify an antigen-triggered mechanism that actively promotes T cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott -Aldrich syndrome Protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T cell activation, WASP is degraded, leading to cytoskeletal rearrangement and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell-APC synaptic contact.