Intestinal cells surprisingly active in pursuit of nutrition and defense

June 29, 2009

Every cell lining the small intestine bristles with thousands of tightly packed microvilli that project into the gut lumen, forming a brush border that absorbs nutrients and protects the body from intestinal bacteria. In the June 29, 2009 issue of the Journal of Cell Biology (www.jcb.org), Matthew McConnell, Matthew Tyska, and colleagues now find that microvilli extend their functional reach even further using a molecular motor to send vesicles packed with gut enzymes out into the lumen to get a head start on breaking down their substrates.

Microvilli have traditionally been viewed as passive scaffolds that increase the surface area of the gut wall. The apical plasma membrane tightly wraps around each protrusive bundle of actin, providing more space for nutrient processing and absorption. The motor protein myosin-1a (myo1a) maintains this structure by connecting the plasma membrane to the actin filaments.

In 2007, Tyska and colleagues found that myo1a functions in isolated brush borders to actively move membrane along the length of the microvilli, like a "membrane escalator." To their surprise, at the top of these escalators--the tips of the microvilli--the membrane pinched off to form small vesicles that were released into the surrounding medium. According to Tyska, when they showed their data to gastroenterologists, they immediately asked "Why would brush borders do that? They're wasting perfectly good apical membrane!" Tyska therefore wanted to see if vesicle shedding was a bona fide physiological function for microvilli.

Sure enough, scanning electron micrographs of rat intestines showed protrusions at the tips of microvilli that looked similar to budding vesicles. And a look at the gut's contents revealed vesicles enriched in the brush border enzyme intestinal alkaline phosphatase (IAP). The vesicles were packed with classical brush border membrane proteins such as aminopeptidases and sugar-processing enzymes, suggesting that the vesicles were derived from microvilli. The vesicles also contained several proteins such as annexin A13 that bend cell membranes and could form part of the vesicle budding machinery.

One protein definitely involved in vesicle formation is myo1a. Myo1a knockout mice still produce lumenal vesicles but they are irregularly sized and no longer enriched in specific proteins like IAP. Tyska thinks that these knockout vesicles are actually chunks of microvillar membrane that are nonspecifically shed when myo1a isn't present to keep them attached to the actin core.

Returning to the gastroenterologists' question: Why would brush borders do that? McConnell et al. showed that the packaged enzymes were exposed on the vesicles' outer surface and were catalytically active. Releasing the enzymes in vesicles might increase their mixing with substrates in the gut's contents. Tyska is particularly interested in IAP, which has recently been shown to detoxify the bacterial outer-membrane component lipopolysaccharide. Releasing IAP in lumenal vesicles could be an important defense mechanism against intestinal pathogens.
-end-
About the Journal of Cell Biology

Founded in 1955, the Journal of Cell Biology (JCB) is published by the Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jcb.org or visit the JCB press release archive at http://www.eurekalert.org/jrnls/rupress.

McConnell, R.E., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200902147.

Rockefeller University Press

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.