March 18, 2011

Protein combos keep cells straight

Researchers define the protein interactions that establish our organs’ lining.

Cryosection of human small intestinal mucosa, showing a villus. Villi are finger-like projections which increase the surface area of the intestine, improving the efficiency of food absorption. (Wellcome Images)

The epithelial cells that form our organ linings have distinct sides (e.g., up/down or top/bottom). This polarity is important in nutrient transport and exclusion of harmful agents.

Defects in this polarity can break down these critical boundaries and lead to toxicity or diseases like microvillus inclusion disease, a severe form of neonatal diarrheal disease.

James Goldenring, Joseph Roland and colleagues now show that interactions between the “motor” protein Myosin VB (Myo5B) and multiple Rab proteins are involved in the complex trafficking processes that establish polarity in epithelial cells. The investigators examined the contributions of Rab/Myo5B interactions with specific pathways using Myo5B mutants that lacked the ability to bind to certain Rab proteins.

They found that different combinations of Rab proteins with Myo5B control distinct processes of membrane regulation and trafficking pathways. The findings, reported in the Feb. 15 Proceedings of the National Academy of Sciences, offer insight into disruption of polarized membranes and, potentially, how they might be repaired.