GP96 (also known as GRP94, HSP90b1), a paralogue of HSP90 in the endoplasmic reticulum, acts as a chaperone for some integrines and Toll-like receptors. Macrophages or B-cells from gp96 knockout mice have abrogated function of TLR2, 4, 5, 7 and 9, but not TLR3 (Yang Y et al 2007, Liu B and Li Z 2008, Staron M et al 2010). GP96 interacts with TLRs and integrines via its C-terminal hydrophobic domain, formed by residues 652-678 (Wu S et al 2012). GP96 functions as a V-shaped dimer in ATP-dependent manner, however it remains unclear how ATP hydrolysis-dependent conformational changes of GP96 are regulated (Li Z and Srivastava PK 1993).
GP96 forms a complex with co-chaperone CNPY3, also known as PRAT4A. GP96-CNPY3 promotes the proper post-translational ectodomain folding of TLRs, but not TLR3 (Liu B et al 2010).
Compartment:
plasma membrane,
extracellular region
Atrial natriuretic peptide receptor 2 (NPR2) binds the C-type natriuretic peptide (NPPC, CNP) hormone. Natriuretic peptide hormones can stimulate natriuretic, diuretic, and vasorelaxant activity through the activation of guanylyl cyclases (Koller et al. 1991, Bartels et al. 2004).
Natriuretic peptides A (NPPA) is a hormone playing a key role in cardiovascular homeostasis through regulation of natriuresis, diuresis, and vasodilation. It specifically binds the atrial natriuretic peptide receptor 1 (NPR1) and stimulates its guanylate cyclase activity resulting in cGMP production (Koller et al. 1991, Pandey 2014).
Folded TLR9 dissociates from GP96:CNPY3 complex (Liu B et al 2010) and translocates to the endolysosome with the aid of the membrane protein UNC93b. Here we assume that TLR7 and TLR8 behave in a similar manner.