Listen to your Gut

• The organizational protein complexes of gut microvilli and ear stereocilia are very alike, with each protein subunit of one having an exact counterpart in the other
• Both complexes possess two cadherins, one myosin motor protein, and two scaffolding molecules, which together link the actin-based apical protrusions at their distal tips
• Damage to the ear complex can lead to Usher syndrome, the most common cause of congenital deaf-blindness – but it’s not yet understood why similar damage to the gut complex doesn’t cause an equally severe phenotype
• Better understanding of these complexes may lead to easier diagnosis of genetic disease, or may help us discover useful information for its treatment

Members of the Zhang laboratory (from left to right: Mingjie Zhang, Jianchao Li, Yunyun He, Qing Lu).

When considering the function of the ear, the gut doesn’t automatically come to mind as a research model. After all, what could two such different tissues have in common? Unexpectedly, the answer lies in some of the most vital functional components of each organ – namely, the gut microvilli and the stereocilia of the ear. These two structures behave in very different ways; while the job of the microvilli is to add surface area to the intestinal epithelium and function in nutrient absorption, stereocilia are responsible for hearing and balance. But what they share is the protein complex that organizes them. Although ear and gut use different complexes, each protein subunit in one has an exact counterpart in the other – one of which even derives from the same gene in both tissues. And as if to mirror this duplication of complexes, two groups published similar findings at the same time in the journal Developmental Cell (1,2). We spoke to Scott Crawley from Vanderbilt University and Jianchao Li from Hong Kong University of Science and Technology to find out more about the organizational proteins of both gut and ear.

An immunofluorescence image of the gut microvilli (green: myosin-7B, red: F-actin cytoskeleton; yellow: colocalization).

Members of the Tyska laboratory (from left to right: David Shifrin, Scott Crawley, Meredith Weck, Suli Mao, Nathan Grega-Larson, Matthew Tyska).

A diagram of the protein organizational complexes in the intestinal microvilli.

Scott Crawley is a postdoctoral trainee in the Matthew Tyska laboratory of the Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, USA. Jianchao Li is a postdoctoral researcher in the Mingjie Zhang laboratory at Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.

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References

1. J Li et al., “Mechanistic basis of organization of the harmonin/USH1C-mediated brush border microvilli tip-link complex”, Dev Cell, 36, 179–189 (2016). PMID: 26812017
2. SW Crawley et al., “ANKS4B is essential for intermicrovillar adhesion complex formation”, Dev Cell, 36, 190–200 (2016). PMID: 26812018.

About the Authors

Jianchao Li

Jianchao Li is a postdoctoral researcher in the Mingjie Zhang laboratory at Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.

More Articles by Jianchao Li

Scott Crawley

Scott Crawley is a postdoctoral trainee in the Matthew Tyska laboratory of the Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, USA.

More Articles by Scott Crawley