Molecular Mechanism of Mucin Secretion: I. The Role of Intragranular Charge Shielding

Abstract

Mucus is an ubiquitous polymer hydrogel that functions as a protective coat on the surface of integument and mucosa of species ranging from simple animals (such as coelenterates) to mammals. The polymer matrix of mucus is made out of long-chain glycoproteins called mucins that are tangled together, forming a randomly woven, highly polyionic network (Lee et al., 1977; Verdugo et al., 1983). Mucin-containing granules, produced by mammalian goblet cells in vitro, undergo massive post-exocytotic swelling. Their swelling kinetics is similar to the swelling of condensed artificial polymer gels (Verdugo, 1984; Tanaka and Fillmore, 1979). We had proposed that mucins must be condensed in the secretory granule and expand by hydration during or after exocytosis (Verdugo, 1984; Tam and Verdugo, 1981). However, the polyionic charges of mucins prevents condensation unless they (the mucins) are appropriately shielded. The present experiments were designed to assert the presence of an intragranular shielding cation and its role in secretion. Giant mucin granules of the slug (Ariolimax columbianus) are released intact from mucus-secreting cells of the slug's skin. They burst spontaneously outside the cell, forming, upon hydration, the typical slug mucus (Deyrup-Olsen et al., 1983). We report here that these granules contain from 2.5 to 3.6 moles calcium/kg dry material, and that calcium is released from the granules immediately before the burst that discharges their secretory product. Therefore, we propose that calcium functions as a shielding cation of polyionic mucins, and that the bursting discharge of mucins from secretory granules must result from the release of calcium from the intragranular compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

The relative contribution of calcium, zinc and oxidation-based cross-links to the stiffness ofArion subfuscusglue

“…The sudden mixing of these moieties could initiate glue formation. Luchtel et al (Luchtel et al, 1984) did not report the methods they used to detect calcium, and it is surprising that all the mucopolysaccharide-releasing cells are not identified as calcium containing, as there must be shielding charge on the polyanions to keep them condensed (Verdugo et al, 1987). Most histological methods are designed to detect insoluble calcium crystals rather than soluble calcium associated with polymers (Humason, 1979), so it is likely that soluble calcium would not have been detected.…”

“…The primary adhesive gland cells in another slug, Ariolimax columbianus, appear to contain calcium (Luchtel et al, 1984). Verdugo et al (Verdugo et al, 1987) found that calcium made up over 10% of the dry material (2.5-3.6molCa…”

The tube cement of Phragmatopoma californica: a solid foam

“…A common feature of secretory granule formation is the condensation of a polyanionic matrix through crosslinking by multivalent cations. Two well-studied examples are the condensation in mast cells of negatively charged heparin glycosaminoglycan by histamine, a divalent cation (Nanavati and Fernandez, 1993;Verdugo et al, 1987); and the condensation in goblet cells of the negatively charged mucin glycoprotein by Ca 2+ (Verdugo, 1990). It follows that condensation of the cement into dense secretory granules may occur by interaction of the anionic polyphosphoserine protein with polycationic Pc1, Pc2, Ca …”

“…The large excess of monovalent Na + could displace some of the multivalent cations crosslinking the polyphosphoserine matrix, leading to the rapid absorption of water (Verdugo et al, 1987). This sudden thirst may contribute to removing water at the interface with the substrate to facilitate the underwater adhesion of the cement proteins to the substrate, particularly the DOPA residues of Pc1 and 2 (Waite, 2002).…”

News from the End of the Gut-How the Highly Segmental Pattern of Colonic HCO3- Transport Relates to Absorptive Function and Mucosal Integrity

“…92) Upon exocytosis, mucins rapidly expand their volume by 1000-fold, 93) and this process was suggested to be driven by electrostatic repulsion of negative charges unmasked during exocytosis. This would necessitate HCO 3 Ϫ , which would raise pH by sequestration of protons, thereby leaving the anionic charges of the mucins unshielded.…”