Expression and potential biological role of α(1,2)fucosylated glycotopes on amniotic and seminal fibronectins

Abstract

The present paper describes concisely the expression and role of α(1,2)-linked fucose on some glycoconjugates as well as the detection, distribution and potential role of that glycotope on human soluble plasma and cellular fibronectins in addition to the expression on both normal and pathological amniotic fluid and seminal plasma fibronectins. The determination of α(1,2)fucosylated glycans is considered with respect to its usefulness as a potential clinically applicable biomarker in obstetrics to monitor pregnancy and in andrology to evaluate the ejaculate of infertile men and in vitro fertilization.

Identification of Soluble Supramolecular FN-fibrin Complexes in Human Plasma

“…[2,6] Structurally, FN is highly heterogenic because of inclusion of alternatively spliced extra domains A and B into the cell-derived FN exclusively, and a non homologous variable connecting segment IIICS into plasma and some cellular FNs, [7,8] and, moreover, of different degree of posttranslational N and O types of glycosylation. [9,10] Disulfide cross-linking of two FN polypeptides at their C-termini ends makes the FN molecule elastic, flexible and able to change conformation from the globular form of plasma FN to extended fibrillar of extracellular matrix. [3] Any alterations of FN conformation caused by binding of FN ligand/s, and/or by posttranslation modifications, including its fragmentation by proteases, [11−13] has been reported to disturb FN domain arrangement, can alter tissue architecture, affecting biological activities and cellular communication, and can lead in turn to tissue dysfunctions.…”

Terminal glycotope expression on milk fibronectin differs from plasma fibronectin and changes over lactation

“…The extent and type of FN glycosylation depend on glycoprotein origin and pathophysiological status [9,10]. The plasma and cellular FNs differ particularly in the amount of N-and O-linked glycans, number of antennae, and terminal sialic acid and fucose expression.…”

“…Plasma-derived FN N-glycans can be di-and triantennary, sialylated and very slightly or nearly absent α1,6-fucosylated. In contrast, cellular FN has diantennary glycans, largely α1,6-fucosylated, but weakly sialylated [5,8,10]. The O-glycan (α2,3-sialylated Galβ1,3GalNAc-) attached to the hexapeptide VTHPGY, in the variable region of alternative-spliced FN, forms an extra domain commonly called the oncofetal IIICS epitope which is one of the effective markers for preterm delivery [8,10,11].…”

“…FN glycans are important for adhesion and host tissue colonization by Borrelia burgdorferi (which causes human Lyme disease) [12], Campylobacter fetus and Campylobacter jejuni (the most frequent bacterial causes of gastrointestinal disease and diarrhea) [13,14], and Streptococcus pneumoniae (the etiological agent of pneumonia) [15]. Moreover, the α1,2-fucosylated FN isoform of amniotic fluid might play a critical role in protecting the fetus and female reproductive routes against pathogenic bacteria [10], which can colonize female tissues. Soluble fucosylated FN may decoy binding sites for pathogens, thus inhibiting pathogen binding to host cell ligand [10,14,15].…”

“…Moreover, the α1,2-fucosylated FN isoform of amniotic fluid might play a critical role in protecting the fetus and female reproductive routes against pathogenic bacteria [10], which can colonize female tissues. Soluble fucosylated FN may decoy binding sites for pathogens, thus inhibiting pathogen binding to host cell ligand [10,14,15]. However, to date there are no reports concerning the fucosylation and sialylation patterns of human milk FN over lactation and its possible roles.…”