Text:

Introduction: The genetically related gel forming mucins, MUC2 (intestine), MUC5B (airways), MUC5AC (airways, stomach) and MUC6 (stomach) have large sizes with heavily glycosylated mucin domains in the central part. The C-termini form intermolecular dimers. The N-terminal regions are evolutionarily similar with identical domain organization important for the oligomerization. MUC5B is vital for normal mucociliary clearance of the lungs whereas MUC2 in colon forms an inner dense and attached stratified layer impermeable to bacteria, and an outer loose and unattached layer habituating commensal bacteria. The MUC2 N-terminus (D1-D2-D′D3 domains) was shown to form concatenated polygone-structures under low pH- and high calcium conditions (1).
The Aim is to understand the cellular packing of the MUC5B and MUC2 mucins and how this influences their secretion.
Method: The N-terminal and D´D3 domains of MUC2 and MUC5B were expressed, purified and then analyzed by subsequent gel filtration, transmission electron microscopy and single particle image processing.
Results: MUC5B multimerizes by disulfide bonds between the D3-domains giving the MUC5B polymer a linear structure (2). Analysis of the MUC5B N-terminus at lower pH and higher calcium concentration revealed a tight dimer+dimer packing where the second dimer is turned upside down by 180 degrees and then slightly rotated. This way of packing the MUC5B in the granulae will allow a slow unwinding of a linear molecule.
Conclusion: The MUC5B and MUC2 mucins are packed in the mucin granulae in a way allowing the formation of linear strands or net-like structures, respectively.

References:
1. Ambort, D., Johansson, M. E. V., Gustafsson, J. K., Nilsson, H., Ermund, A., Johansson, B. R., Koeck, P. J. B., Hebert, H., and Hansson, G. C. (2012) Proc. Natl. Acad. Sci. U. S. A. 109, 5645-5650
2. Ridley, C., Kouvatsos, N., Raynal, B. D., Howard, M., Collins, R. F., Desseyn, J. L., Jowitt, T. A., Baldock, C., Davis, C. W., Hardingham, T. E., and Thornton, D. J. (2014) J. Biol. Chem. 289, 16409-16420

Figures:

MUC2 N-terminal Polygon Formation, 2D Representation

MUC2 – Intestinal Goblet Cells, Mucus Secreted as a Net

MUC5B N-terminal Dimer Formation, 3D Representation

MUC5B-Airway Submucosal Glands, Mucus Secreted as Strands

« Back to The 16th European Microscopy Congress 2016

EMC Abstracts - https://emc-proceedings.com/abstract/the-supramolecular-packing-of-the-gel-forming-muc5b-and-muc2-mucins-and-its-importance-for-cystic-fibrosis/