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. 2020 Oct 29;11:573372. doi: 10.3389/fphys.2020.573372

FIGURE 3.

FIGURE 3

Proposed model of NKLAM function in NK cells. The cytolytic granules of resting NK cells contain little to no NKLAM. Upon cytokine exposure or target stimulation, activated NK cells rapidly transcribe and translate NKLAM, which is embedded in cytolytic granule membranes. Smaller, intragranular vesicles also have NKLAM in their membranes. NK-tumor interaction releases granule contents (perforin, granzymes) into the tumor cell at the immunological synapse. Intragranular vesicles are also released; these now called extracellular vesicles (EVs) contain NKLAM, as well as perforin and granzymes, and enter the tumor cell by endocytosis. Granzymes induce caspase activation; NKLAM ubiquitinates and degrades the tumor survival protein UCKL-1. This combination of perforin, granzymes, and NKLAM ensures death of the tumor cell. Red circles: EVs; gray bars: NKLAM; green squares, blue ovals: cytolytic proteins granzymes A and B; yellow bars: perforin; purple bar: UCKL-1; yellow circles: ubiquitin.