Lytic granule polarization, rather than degranulation, is the preferred target of inhibitory receptors in NK cells.

Inhibitory Receptors in NK Cells Degranulation, Is the Preferred Target of Lytic Granule Polarization, Rather than

Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells

The relative contribution to cytotoxicity of each of the multiple NK cell activation receptors has been difficult to assess. Using Drosophila insect cells, which express ligands of human NK cell receptors, we show that target cell lysis by resting NK cells is controlled by different receptor signals for cytolytic granule polarization and degranulation. Intercellular adhesion molecule (ICAM)-1 o...

β2 integrin induces TCRζ-Syk-phospholipase C-γ phosphorylation and paxillin-dependent granule polarization in human NK cells.

Cytotoxic lymphocytes kill target cells through polarized release of the content of lytic granules at the immunological synapse. In human NK cells, signals for granule polarization and for degranulation can be uncoupled: Binding of β(2) integrin LFA-1 to ICAM is sufficient to induce polarization but not degranulation, whereas CD16 binding to IgG triggers unpolarized degranulation. In this study...

NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing

Natural killer (NK) cell activation triggers sequential cellular events leading to destruction of diseased cells. We previously identified lytic granule convergence, a dynein- and integrin signal-dependent movement of lysosome-related organelles to the microtubule-organizing center, as an early step in the cell biological process underlying NK cell cytotoxicity. Why lytic granules converge duri...

Molecular mechanisms of natural killer cell activation.

With an array of activating and inhibitory receptors, natural killer (NK) cells can specifically eradicate infected and transformed cells. Target cell killing is achieved through directed release of lytic granules. Recognition of target cells also induces production of chemokines and cytokines that can coordinate immune responses. Upon contact with susceptible cells, a multiplicity of activatin...