PLA2R1 gene

The PLA2R1 gene (PLA2R1 stands for: Phospholipase A2 Receptor 1) is a human gene that codes for the receptor of the secretory phospholipase A2 (phospholipase A2 receptor/sPLA2). The gene is localized on chromosome 2q24.2. Alternatively spliced transcript variants encoding different isoforms have been identified.

The encoded protein is probably present in both a transmembrane and a soluble form. The transmembrane receptor may play a role in the clearance of phospholipase A2 and thereby inhibit its action. Polymorphisms at this locus have been associated with susceptibility to idiopathic membranous nephropathy.

The protein acts as a receptor for secretory phospholipase A2 (sPLA2-IB/PLA2G1B), but not for sPLA2-IIA/PLA2G2A. Can also bind to PA2-like snake venoms. Although its exact function is still unclear, binding of sPLA2 to its receptor is involved in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2.

The binding of sPLA2-IB/PLA2G1B induces various effects depending on the cell type, such as the activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators and the selective release of arachidonic acid in bone marrow-derived mast cells.

In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in the production of proinflammatory cytokines during endotoxic shock.

Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities.

The soluble secretory phospholipase A2 receptor form circulates and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B (Granata F et al. 2005). In podocytes, sPLA2-IB/PLA2G1B binding can regulate podocyte survival and glomerular homeostasis (Pan Y et al. 2014).

Diseases associated with PLA2R1 include:

• primary membranoproliferative glomerulonephritis
• and
• membranous nephropathy.

Associated signaling pathways include glycerophospholipid biosynthesis and acyl chain remodeling of PE.

1. Granata F et al. (2005) Activation of cytokine production by secreted phospholipase A2 in human lung macrophages expressing the M-type receptor. J Immunol 174:464-474)
2. Pan Y et al. (2014) sPLA2 IB induces human podocyte apoptosis via the M-type phospholipase A2 receptor. Sci Rep 4:6660.