Identification of a Mucin and Insulin Secretion “Traffic Control” System

In a recent study, scientists from the Center for Genomic Regulation (CRG) in Barcelona investigated how cells execute the controlled release of mucins and insulin, two vital proteins for human health. Their findings were published in the journal Nature Communications.

Mucins: Guardians of Barrier Defense and Lubrication, Crucial for Respiratory and Digestive Health

Mucins, the main mucus components, are essential for creating barrier defenses and lubricating bodily surfaces, including the digestive and respiratory systems. To ensure adequate levels for healthy biological activities, specialized cells govern the controlled release of about one liter of mucins daily.

“An imbalance in mucin secretion, whether excessive or inadequate, can lead to respiratory and digestive tract diseases ranging from chronic obstructive pulmonary disease (COPD) to ulcerative colitis,” explains José Wojnacki, the study’s first author and a postdoctoral researcher at the Center for Genomic Regulation. Similarly, the hormone insulin, released by the pancreas, is essential for controlling blood glucose levels. Problems with insulin synthesis mostly bring on diabetes.

Cellular Gatekeepers: Tetraspanin-8 Regulates Release of Mucins and Insulin from Protein Granules

Proteins, including mucins and insulin, are kept as “granules” within cells. When these substances must be released, the granules adhere to the membrane outside the cell and discharge their contents into the surrounding space. According to the study, the cell membrane protein tetraspanin-8 is a gatekeeper during secretion by controlling which granules containing mucin or insulin bind to the membrane and when.

The research shows that mucin and insulin secretion are controlled in two stages. Pre-docked granules are released quickly at first, and then granules from a reserve pool are released more slowly. Additionally, a protein known as syntaxin-2 is necessary for fusing granules containing mucins.

Tetraspanin-8 participates in the sequestration of syntaxin-2, which regulates mucin release. Because more syntaxin-2 is accessible for granule docking and fusion without tetraspanin-8, the researchers saw a doubling of mucin secretion. This finding extends to insulin release and suggests a general process that has important ramifications for our knowledge of how cells secrete these essential proteins in response to physiological demands.

Cellular Traffic Control: Tetraspanin-8 Governs Syntaxin-2 to Regulate Release of Mucins and Insulin

Vivek Malhotra, a researcher at the Center for Genomic Regulation and an ICREA Research Professor, offers an analogy: If the cell is a busy metropolis, the granules are lorries loaded with commodities like mucins and insulin. Proteins like syntaxin-2 are responsible for opening the city’s gate to the outer world.

Tetraspanin-8, in this comparison, regulates the quantity of syntaxin-2 molecules available to open gates so that trucks can dock and export their cargo, acting as traffic control at the city’s edge. Based on physiological requirements, this regulated management ensures that the precise amount of mucins or insulin is released.

Dr. Malhotra continues, “Tetraspanin-8 is an easy target for developing chemicals to control its function and, therefore, a means to reset deregulated mucin and insulin secretion noted in the associated human pathologies.”

Tetraspanin-8’s function is currently being examined in sophisticated models that simulate the intricate physiology of the colon, airways, and pancreas. This will make it easier to comprehend how different cells may contribute to regulating the net secretion of mucins and insulin.

Read the original article on PHYS.

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