Title: Golgi Redox and Gut Health: the Elegant Mechanism for ConstructingIntestinal Mucus
Guest: Deborah Fass, Departmentof Chemical and Structural Biology, WeizmannInstitute of Science
Threats to the body’s physical integrity come in a varietyof forms: pathogens, chemical poisons and irritants, and mechanical injuries.Early in animal development, a multifunctional safety net evolved to protectagainst such hazards. This safety net is built of the mucus hydrogels that coverand shield the hundreds of square meters of vulnerable epithelia in the body,most notably in the lungs and intestines. Mucus forms by disulfide bond cross-linkingof enormous glycoproteins called “mucins.” Using X-ray crystallography andcryo-electron microscopy, we determined structures of the region of theintestinal mucin involved in cross-linking. These structures revealed how themucus scaffold is organized and led us to the discovery that mucus protectsagainst even more dangers than was previously appreciated. In parallel, wefound that a catalyst of disulfide bond formation in the Golgi apparatus isnecessary for constructing functional mucus, but, surprisingly, not for carryingout the actual cross-linking. Instead, disulfide bonding in the Golgicontributes to mucus functionality in an unexpected manner, revealing a newcell biological principle likely to be relevant to other processes in additionto mucus production.
Host: Sagi Levy