Molecular mechanism of mucin secretion: I. The role of intragranular charge shielding

P Verdugo, I Deyrup-Olsen, M Aitken… - Journal of dental …, 1987 - journals.sagepub.com
P Verdugo, I Deyrup-Olsen, M Aitken, M Villalon, D Johnson
Journal of dental research, 1987journals.sagepub.com
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 …
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 poly ionic mucins, and that the bursting discharge of mucins from secretory granules must result from the release of calcium from the intragranular compartment. Calcium release would unshield the polyionic charges of mucins, driving the mutual repulsion of polymer chains and triggering a quick expansion of the mucin network (resembling a Jack-in-the-box mechanism).
The existence of a poly ion associated with a shielding cation seems to be a common feature in a large variety of secretory granules. Thus, the proposed spring-loaded release system based on the unshielding of a condensed polyion may serve as a general model for explaining the molecular mechanism of product release in secretion.
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