August 5, 2021

Motor protein linked to intestinal cell differentiation

The motor protein MYO5B, a cause of the congenital intestinal disorder microvillus inclusion disease, does more than move cellular cargo, Vanderbilt researchers have discovered.

Microvillus inclusion disease (MVID) is a congenital intestinal disorder resulting in malabsorption and diarrhea. MVID can be caused by the loss of function in MYO5B, a motor protein that moves enzymes and transporters to the intestinal surface for nutrient uptake.  

In a paper published last month in the journal JCI Insight, Izumi Kaji, PhD, and colleagues report that MYO5B does more than move proteins. It alters the differentiation of cell populations that are essential for normal intestinal function.  

Loss of MYO5B in a mouse model led to an increase in immature Paneth cells, which regulate intestinal stem cell function, and a decrease in tuft cells, which sense luminal contents. This highlights the importance of MYO5B in maturation of stem cells in the intestine.  

The researchers found that treatment with the signaling molecule LPA (lysophosphatidic acid) or inhibition of the Notch signaling pathway increased tuft cell populations and promoted cell differentiation. 

These findings reveal a greater breadth of MYO5B function and suggest potential approaches for the treatment of MVID.

This research was supported by National Institutes of Health grants DK048370, DK118640, DK070856, and a pilot grant from the Vanderbilt Digestive Diseases Research Center.