Late steps in secretory lysosome exocytosis in cytotoxic lymphocytes

Abstract

Natural Killer cells are a subset of cytotoxic lymphocytes that are important in host defense against infections and transformed cells. They exert this function through recognition of target cells by cell surface receptors, which triggers a signaling program that results in a re-orientation of the microtubule organizing center and secretory lysosomes toward the target cell. Upon movement of secretory lysosomes to the plasma membrane and subsequent fusion, toxic proteins are released by secretory lysosomes in the immunological synapse which then enter and kill the target cell. In this minireview we highlight recent progress in our knowledge of late steps in this specialized secretion pathway and address important open questions.

Keywords: degranulation; endosomes; lytic granules; maturation; secretory lysosomes.

Figure 1

Maturation and fusion. Pathways and proteins regulating various aspects of the maturation and fusion of secretory lysosomes (see text for details). PM denotes plasma membrane, IS immunological synapse.

Figure 2

Domain architecture of munc13-4. The C2B domain was modeled on the munc13-2 C2B domain structure (26). Note the rab27-binding domain at the junction between C2B and MUN domain.