Sorting and export of mucins.

Inflammatory Bowel Diseases (IBD) affected more than 6.8 million people worldwide in 2017, and Chronic Obstructive Pulmonary Disease(COPD) caused 3.23 million deaths in 2019.

Both illnesses present a disturbance in the quantity and quality of mucus due to an abnormal expression and secretion of mucins. The mucins are the main component of mucus and are specifically expressed in cells and tissues. Mucin secretion is crucial for the normal physiology of wet mucosal epithelium.

Growing data shows that alterations in mucins expression and their localization are related to pathological processes, such as inflammation, infection, autoimmunity, and cancer.

All mucins are synthesized in the endoplasmic reticulum and exported to the Golgi complex, and after extensive glycosylation, are transported to the plasma membrane.

However, how these mucins are sorted and packed into granules that can reach micrometers in size remains largely unknown.

I hypothesize that transmembrane and secreted mucins are sorted and packed in separate containers by regulatory partners, different from those involved in other bulky-cargo pathways – as collagen –. The Malhotra lab is a world-leader in the study of protein secretion.

Recently, I have tagged mucins with fluorescent proteins by CRISPR/Cas9 gene-editing technology, which will allow me to understand these glycoproteins from synthesis to functional target.

Unveiling this fundamental knowledge could stimulate the development of therapies aimed to modulate the expression and precise release of mucins, both in pathologies due to mucin hyposecretion – such as IBD – and hypersecretion – observed in COPD –.