GNLY binds the bacterial cell surface in the phagosome

Stable Identifier
R-HSA-6807578
Type
Reaction
Species
Homo sapiens
Compartment
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Summation

Granulysin (GNLY), an antimicrobial protein, is produced by activated human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells (Pena SV et al. 1997; Stenger S et al. 1998; Ogawa K et al. 2003). GNLY is synthesized as a 15-kDa molecule and then proteolytically cleaved at the amino and carboxyl termini to produce a 9-kDa form (Pena SV et al. 1997; Hanson DA et al. 1999). The 9?-kDa form of GNLY is confined to cytolytic granules that are directionally released by receptor-mediated granule exocytosis following target cell recognition (Hanson DA et al. 1999; Clayberger C et al 2012). In contrast, the 15-kDa form is constitutively secreted from distinct granules that lack perforin and granzyme (Clayberger C et al 2012). The secreted 9-kDa GNLY is active against a range of intracellular pathogens, such as Listeria innocua, Mycobacterium tuberculosis and Trypanosoma cruzi (Stenger S et al. 1998; Walch M et al. 2005). The secreted GNLY is thought to bind to lipid rafts in eukaryotic cell membranes, where it is taken up and delivered to the early sorting endosomes which afterwards fuse with bacteria-containing phagosomes, where the GNLY-mediated lysis of bacteria is induced (Stenger S et al. 1998; Barman H et al. 2006; Walch M et al. 2005, 2007). Perforin is thought to promote GNLY-mediated bacteriolysis by an increase in endosome-phagosomes fusion triggered by an intracellular Ca(2+) rise (Walch M et al. 2007). However, it was also suggested that GNLY may require perforin as a cofactor to enter the host cells (Stenger S et al. 1998).

It is believed that the electrostatic interaction between the cationic GNLY and the negatively charged microbial cell surface increases the ability of GNLY to fold into amphipathic conformation which can disrupt microbial membranes resulting in cytolysis by osmotic shock (Wang Z et al. 2000; Ernst WA et al. 2000; Anderson DH et al. 2003; Barman H et al. 2006).

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