February 8, 2016

Building intestinal brush borders

Studies of the molecular complex that helps build specialized cellular surfaces could shed light on the mechanisms underlying a genetic deaf-blindness syndrome accompanied by intestinal disease.

(Wellcome Images)

The epithelial cells that line our intestines build a special surface called the “brush border,” which is critical for absorbing nutrients and defending against pathogens.

Matthew Tyska, Ph.D., and colleagues previously discovered that the brush border’s densely packed microvilli – finger-like membrane protrusions – are connected to each other via cadherin adhesion molecules. Now, the investigators have demonstrated a critical role for a protein called ANKS4B in stabilizing the cadherin-based adhesions between microvilli to build a normal brush border.

They further show that ANKS4B interacts with another scaffolding-type protein (USH1C) and with a motor protein (MYO7B). The gut adhesion complex is similar to the complex linking stereocilia that cover inner ear hair cells, which are responsible for hearing and balance. Genetic mutations in USH1C cause Usher syndrome, a form of inherited deaf-blindness accompanied by intestinal disease.

The findings, reported in the Jan. 25 issue of Developmental Cell, reveal the molecular interactions that drive microvillar adhesion and may shed light on the mechanisms underlying sensory and intestinal dysfunction in patients with Usher syndrome.

This work was supported by the American Heart Association, the Vanderbilt Digestive Disease Research Center, and the National Institutes of Health (grants DK075555, DK095811).

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