Nacho average organ: The UberEATs driver of the small intestine

Warning: you may or may not be hungry after reading this. 

Everyone loves a good plate of nachos, right? The most convenient kind are delivered by UberEATs. Each bite is carefully organized to somehow include all the toppings you ordered: chunks of tender chicken, sweet yellow corn, black beans, guacamole, and of course, you can’t forget the flowing river of queso. But when you have gastrointestinal (GI) issues, what may start as a party in your mouth ends with a long intimate night on the toilet, accompanied with good ole gastric distress. 

To help understand and prevent GI issues that can ruin a Taco Tuesday night, Amy Engevik, Ph.D., assistant professor in the Regenerative Medicine and Cell Biology, and her lab study GI diseases and disorders. One specific project focuses on the organization and delivery system of one of the most important organs in the digestive system: the small intestine.

This organ’s name is deceiving, as the small intestine is anything but small. It is around 23 feet long, about three times the average person’s height. Additionally, the total surface area is roughly 2,700 square feet. Yes, you read that right, 2,700 square feet. That’s three times bigger than the average rental apartment and large enough to cover a tennis court!

So, at this point you might be wondering… how does this not-so-small organ fit within our abdomen? 

"One possible UberEATs driver that delivers the IMAC is Myosin 5b, an important molecular motor."

-- Sarah Dooley

This is where the organization of the small intestine can be appreciated. It’s carefully folded, and its lining is decorated with 130 billion finger-like projections called microvilli that together create the intestinal brush border, providing an enormous intestinal surface area. That massive surface area is critical because it maximizes the small intestine’s primary function: nutrient and water absorption. 

Without the proper assembly of all these microvilli, you can become malnourished no matter how much food you chow down. You’ve probably heard or used the phrase “food goes right through me!” Everything you put in just comes right back out at the other end. This is an event I probably don’t have to describe to you. However, it is important to note that many patients who live with digestive diseases and disorders like Crohn’s disease and irritable bowel syndrome (IBS) regularly experience this phenomenon alongside other discomforting conditions.

To alleviate or cure GI issues like malnutrition and chronic intestinal inflammation, basic science researchers can study the brush border and microvilli very closely. By doing so, GI experts have discovered that the organization of the intestinal brush border is reliant on the integrity and proper packing of microvilli. A disorganized brush border is postulated to impact intestinal permeability, or a leaky gut, and leave individuals more susceptible to infections.

To optimally function, microvilli organization and packing is achieved through transport systems run by molecular motors. These systems are much like an UberEATs delivery: the cargo (nachos for instance) is trafficked to its correct destination, the front door. In the small intestine, molecular motors deliver important cargo, like protein complexes, to microvilli to facilitate dense packing, helping make absorption possible. 

One important protein complex is the intermicrovillar adhesion complex (IMAC). When delivered, this protein complex forms thread-like-linkages and connects the microvillar tips together. However, in Crohn’s disease patients, the IMAC fails to reach the microvillar tips. Without proper IMAC trafficking and assembly, the organization and integrity of microvilli is lost, resulting in insufficient nutrient absorption and the development of severe intestinal damage.

But what molecular motor delivers the IMAC in a healthy individual in the first place? No one knows. This is one of the basic science questions my lab seeks to understand and answer.

One possible UberEATs driver that delivers the IMAC is Myosin 5b, an important molecular motor. Our lab and others have previously shown that Myosin 5b is found at the base of the brush border and plays a vital role in nutrient and water absorption by delivering important cargo to the tips of microvilli, like critical ion transporters.

We are currently examining the localization of IMAC proteins and microvillar integrity when the Myosin 5b motor is nonfunctional. By understanding the UberEATs driver of the small intestine – the molecular motor that traffics IMAC in a healthy individual – we may be on the right road to design therapeutics to prevent and/or treat patients experiencing GI issues, like Crohn’s disease.