The Endocytic Process

Our cells constantly engulf macromolecules, internalize ligand-bound receptors, and recycle the plasma membrane itself. The correct regulation of these processes is essential for the health of cells and the animal they form.

Using unbiased genetic screens in C. elegans, Gunther Hollopeter, Molecular Medicine, has identified conserved regulators of the core endocytic machinery. Hollopeter is employing a multipronged approach to characterize their mechanisms of action at the molecular, cellular, and organismal levels.

At the heart of the endocytic process lies the AP2 clathrin adaptor complex, which appears to undergo a conformational change during vesicle formation to actively couple membrane and cargo to the clathrin coat. Despite the central role of AP2, there is a lack of critical details about how this molecular machine is regulated in vivo and how this regulation influences multicellular systems. Hollopeter is using innovative tools that allow him to quantify AP2 activity at multiple levels and is employing deep genetic screens to identify protein families that appear to govern AP2 conformation and activity.

Understanding the fundamental cellular machinery may inform rational design of better therapeutics to treat diseases believed to have an underlying endocytic component, such as cancer, influenza, hepatitis, cardiovascular, and Alzheimer’s.

NIH Award Number: 1R01GM127548-01A1

Cornell Researchers

Funding Received

$1.83 Million spanning 5 years