January 10, 2013

The idea of screening for something valuable is something we’ve all done. When looking for a dog several years ago, I screened through PetFinder to find the exact dog I wanted to bring home based on size, age, scruffiness, etc. Despite the fact that this dog just farted at my feet, my PetFinder screen brought me to my best friend. For a biologist, screening can lead to exciting discoveries about what genes are important in a specific process (minus the gas, I think).

During endocytosis, a cell takes in material from its outside environment. Clathrin-mediated endocytosis involves the inward budding of vesicles, and depends on a lattice, or “coat”, of clathrin molecules that help shape the rounded vesicle. A recent paper describes the results of a screen to find regulators of clathrin-coated vesicle formation at the plasma membrane, one of the earliest steps in clathrin-mediated endocytosis. Kozik and colleagues screened the entire human genome for regulators, and found 92 genes that affect this process. One of these genes encodes the protein V-ATPase, which is found in many membranes and can pump protons across a membrane to regulate pH. In the images above, V-ATPase-inhibited cells (bottom) formed enlarged clathrin-coated structures, compared to the small and uniform clathrin-coated vesicles in control cells (top). Kozik and colleagues found that V-ATPase inhibition blocked the recycling of cholesterol back to the plasma membrane, where it has been suggested that cholesterol aids in membrane bending.

 BONUS!! Electron microscopy image of a heart-shaped vesicle, acquired as part of the screen to find clathrin regulators.

Kozik, P., Hodson, N., Sahlender, D., Simecek, N., Soromani, C., Wu, J., Collinson, L., & Robinson, M. (2012). A human genome-wide screen for regulators of clathrin-coated vesicle formation reveals an unexpected role for the V-ATPase Nature Cell Biology, 15 (1), 50-60 DOI: 10.1038/ncb2652  
Adapted by permission from Macmillan Publishers Ltd, copyright ©2013