Actin foci facilitate activation of the phospholipase C-γ in primary T lymphocytes via the WASP pathway

Wiscott Aldrich Syndrome protein (WASP) deficiency results in defects in calcium ion signaling, cytoskeletal regulation, gene transcription and overall T cell activation. The activation of WASP constitutes a key pathway for actin filament nucleation. Yet, when WASP function is eliminated there is ne...

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Bibliographic Details
Published in:eLife 2015-03, Vol.4
Main Authors: Kumari, Sudha, Depoil, David, Martinelli, Roberta, Judokusumo, Edward, Carmona, Guillaume, Gertler, Frank B, Kam, Lance C, Carman, Christopher V, Burkhardt, Janis K, Irvine, Darrell J, Dustin, Michael L
Format: Article
Language:English
Subjects:
Actin
actin polymerization
Actins - metabolism
Animals
Antigens
Calcium Signaling
Calcium signalling
Cell activation
Cell adhesion & migration
Cell Biology
Cells, Cultured
Cytoskeleton
Defects
Enzyme Activation
Gene regulation
immunological synapse
Immunological synapses
Immunology
Kinases
Ligands
Localization
Lymphocytes
Lymphocytes T
Medical research
Medicine
Mice
Mice, Inbred C57BL
Morphology
Phospholipase C
Phospholipase C gamma - metabolism
Polymerization
Protein deficiency
Protein-tyrosine kinase
Proteins
Signal transduction
Synapses
T cell receptor signaling
T cell receptors
T-Lymphocytes - enzymology
T-Lymphocytes - metabolism
Transcription
Wiskott-Aldrich Syndrome Protein - metabolism
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Summary:Wiscott Aldrich Syndrome protein (WASP) deficiency results in defects in calcium ion signaling, cytoskeletal regulation, gene transcription and overall T cell activation. The activation of WASP constitutes a key pathway for actin filament nucleation. Yet, when WASP function is eliminated there is negligible effect on actin polymerization at the immunological synapse, leading to gaps in our understanding of the events connecting WASP and calcium ion signaling. Here, we identify a fraction of total synaptic F-actin selectively generated by WASP in the form of distinct F-actin 'foci'. These foci are polymerized de novo as a result of the T cell receptor (TCR) proximal tyrosine kinase cascade, and facilitate distal signaling events including PLCγ1 activation and subsequent cytoplasmic calcium ion elevation. We conclude that WASP generates a dynamic F-actin architecture in the context of the immunological synapse, which then amplifies the downstream signals required for an optimal immune response.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.04953