Mechanically active integrins target lytic secretion at the immune synapse to facilitate cellular cytotoxicity.

ABSTRACT: Cytotoxic lymphocytes fight pathogens and cancer by forming immune synapses with infected or transformed target cells and then secreting cytotoxic perforin and granzyme into the synaptic space, with potent and specific killing achieved by this focused delivery. The mechanisms that establish the precise location of secretory events, however, remain poorly understood. Here we use single cell biophysical measurements, micropatterning, and functional assays to demonstrate that localized mechanotransduction helps define the position of secretory events within the synapse. Ligand-bound integrins, predominantly the α_Lβ₂ isoform LFA-1, function as spatial cues to attract lytic granules containing perforin and granzyme and induce their fusion with the plasma membrane for conte

SUBMITTER: Wang MS 

PROVIDER: S-EPMC9184626 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature