Repository logo

Actin depletion initiates events leading to granule secretion at the immunological synapse.



Change log


Ritter, Alex T 
Asano, Yukako 
Stinchcombe, Jane C 
Dieckmann, NMG 
Chen, Bi-Chang 


Cytotoxic T lymphocytes (CTLs) use polarized secretion to rapidly destroy virally infected and tumor cells. To understand the temporal relationships between key events leading to secretion, we used high-resolution 4D imaging. CTLs approached targets with actin-rich projections at the leading edge, creating an initially actin-enriched contact with rearward-flowing actin. Within 1 min, cortical actin reduced across the synapse, T cell receptors (TCRs) clustered centrally to form the central supramolecular activation cluster (cSMAC), and centrosome polarization began. Granules clustered around the moving centrosome within 2.5 min and reached the synapse after 6 min. TCR-bearing intracellular vesicles were delivered to the cSMAC as the centrosome docked. We found that the centrosome and granules were delivered to an area of membrane with reduced cortical actin density and phospholipid PIP2. These data resolve the temporal order of events during synapse maturation in 4D and reveal a critical role for actin depletion in regulating secretion.



Actins, Cell Membrane, Cells, Cultured, Cytoplasmic Granules, Fluorescent Antibody Technique, Humans, Immunological Synapses, Models, Immunological, Phospholipids, T-Lymphocytes, Cytotoxic

Journal Title


Conference Name

Journal ISSN


Volume Title



Elsevier BV
Wellcome Trust (103930/Z/14/Z)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (75880)
Funding was provided by the Wellcome Trust through Principal Research Fellowships (075880 and 103930) to G.M.G. and a Strategic Award (100140) to the Cambridge Institute for Medical Research (CIMR). A.T.R. is an NIH-OxCam scholar supported by funding to J.L.-S. from the Eunice Shriver National Institute of Child Health and Human Development.