News from CRG
New research reveals how healthy cells in our bodies produce mucins – the main component of mucous, which protects our intestine and airway from pathogens, toxins and allergens. Scientists have already linked defects in mucins secretion to airway and colonic diseases, such as asthma or ulcerative colitis. These new processes discovered by the scientists at the Centre for Genomic Regulation (CRG) in Barcelona in collaboration with researchers at the Pompeu Fabra University, reveal how cells control quantities of mucin released and could become a new avenue to treat several mucin-related diseases.
CRG researchers Gerard Cantero-Recasens and Vivek Malhotra wanted to understand how normal cells secrete mucins in the right quantity and quality, so they can design procedures to correct mucin secretion defects in diseases where either too much or too little mucin is produced, such as asthma, chronic obstructive pulmonary disease, Crohn’s disease and colorectal cancer.
Their data published in the journals eLife and Journal of Biological Chemistry, reveal two proteins called TRPM4 and NCX that work together to control mucin secretion both in healthy cells, and in cells derived from patients with cystic fibrosis. They have also identified a third protein called KChIP3 that senses calcium levels within healthy cells to release mucins, which is crucial to maintain the correct thickness of the mucous layer in the colon. This means cells possess means to control how much mucin they produce depending on the cellular needs. They can produce large amounts if an allergen or pathogen is present, or release it constantly to preserve the mucous layer.
And by studying different cell types, the team discovered the process cells use to control stimulated mucin secretion is the same in both the colon and the airways.
Cantero-Recasens, G., Butnaru, C. M., Valverde, M. A., Naranjo, J. R., Brouwers, N., and Malhotra, V. (2018) KChIP3 coupled to Ca2+ oscillations exerts a tonic brake on baseline mucin release in the colon. Elife. 10.7554/eLife.39729
Cantero-Recasens, G., Butnaru, C. M., Brouwers, N., Mitrovic, S., Valverde, M. A., and Malhotra, V. (2018) Sodium channel TRPM4 and sodium/calcium exchangers (NCX) cooperate in the control of Ca2+-induced mucin secretion from goblet cells. J. Biol. Chem.10.1074/jbc.RA117.000848