Identification of a novel mammalian post-translational modification, phosphocholine, on placental secretory polypeptides

Abstract

Placental neurokinin B appears to be post-translationally modified by phosphocholine (PC) attached to the aspartyl side chain at residue 4 of the mature peptide. Corticotrophin releasing factor (CRF) was found to be expressed by the rat placenta with the main secreted forms being phosphocholinated proCRF+/− one or two polysaccharide moieties. A combination of high-pressure liquid chromatography (HPLC) and two-site immunometric analysis suggested that PC was also attached to the placental precursors of adrenocorticotrophin, hemokinin, activin and follistatin. However, the fully processed forms of rat placental activin and CRF were free of PC. Formerly, the parasitic filarial nematodes have used PC as a post-translational modification, attached via the polysaccharide moiety of certain secretory glycoproteins to attenuate the host immune system allowing parasite survival, but it is the PC group itself which endows the carrier with the biological activity. The fact that treatment of proCRF peptides with phospholipase C but not endoglycosidase destroyed PC immunoreactivity suggested a simpler mode of attachment of PC to placental peptides than that used by nematodes. Thus, it is possible that by analogy the placenta uses its secreted phosphocholinated hormones to modulate the mother's immune system and help protect the placenta from rejection.

Microbial Modulation of Host Immunity with the Small Molecule Phosphorylcholine

“…Even the human host itself can undergo stage-specific modification of proteins with ChoP, such as during pregnancy. It has been shown that placental polypeptides are modified with ChoP, which has been proposed to help shield the fetus from immune recognition (42). In the following sections, the advantages and disadvantages of microbial ChoP expression in different host environments are highlighted.…”

Legionella pneumophila regulates the small GTPase Rab1 activity by reversible phosphorylcholination

“…3 A, lanes 1-3, and B, lane 1). Because detection of the 14 Ccholine incorporated into the target molecules requires at least 3-wk exposure of X-ray films to the gels, we established a Western blot-based detection with the PC-specific antibody TEPC 15 (21). This antibody recognizes both PC-Rab1 and PC-AnkX but not AMP-Rab1 (Fig.…”

Mechanisms of Maternal Immune Tolerance During Pregnancy

“…parasites). In parasites it has been suggested that phosphocholine containing proteins are secreted into host organisms and have an effect on immune cells leading to immunosuppression (Lovell et al, 2007). In particular, phosphocholinated proteins in filarial nematodes have been shown to inhibit normal proliferative responses of both T and B lymphocytes in vitro.…”

“…In the placenta, Lovell et al, (Lovell et al, 2007) showed that a large number of placental polypeptides and proteins carry phosphocholine as a tissue specific post translational modification and suggested the presence of phosphocholine groups on placental secretory proteins and peptides may play a major role in maternal immune tolerance during pregnancy. In these studies, placental neurokinin B and the precursors of corticotropin releasing hormone (CRH), adrenocorticotropin, hemokinin, activin and follistatin were shown to be post-translationally modified by the addition of phosphocholine using a combination of HPLC and two site immunometric analyses.…”