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

Abstract:

: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.

journal_name

Immunity

journal_title

Immunity

authors

Ritter AT,Asano Y,Stinchcombe JC,Dieckmann NM,Chen BC,Gawden-Bone C,van Engelenburg S,Legant W,Gao L,Davidson MW,Betzig E,Lippincott-Schwartz J,Griffiths GM

doi

10.1016/j.immuni.2015.04.013

subject

Has Abstract

pub_date

2015-05-19 00:00:00

pages

864-76

issue

5

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(15)00173-9

journal_volume

42

pub_type

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