Shedding light on the dynamics of endocytosis and viral budding
- Gang Bao†,‡ and
- X. Robert Bao§
- †Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332; and§Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125
Endocytosis is used by eukaryotic cells to perform a wide range of functions, including the uptake of extracellular nutrients and the regulation of cell-surface receptors, as well as by toxins, viruses, and microorganisms to gain entry into cells (1). Endocytosis actually encompasses many different processes, such as phagocytosis of large (>250 nm) particles as well as pinocytosis of large volumes of fluid (2). One of the most important endocytic mechanisms is a receptor-mediated process whereby the plasma membrane binds specific macromolecules and smaller particles by means of specialized receptors, invaginates around those particles, and then pinches off to form small vesicles. Receptor-mediated endocytosis had been thought to be assisted by specific proteins, either clathrin or caveolin, polymerizing into a spherical shell around the invagination (3). Recently, however, evidence has arisen for a different, clathrin- and caveolin-independent route by which endocytosis may occur (4, 5). The understanding and quantitative analysis of the mechanisms underlying receptor-mediated endocytosis have important implications for not only viral pathogenesis but also the delivery of macromolecules and nanoparticles for intracellular imaging and targeted therapies (6).
A Model for Clathrin-Independent Endocytosis
The key process of endocytosis is the formation of the vesicle wrapping the particle, which requires mechanical force. Despite the essential role of endocytosis in biology, much of the mechanics behind it remains elusive. Although clathrin alone can, under certain conditions, assemble into a caged structure, it may not be the major driving force for membrane deformations during endocytosis. The macromolecular assembly with which clathrin associates, however, does contain proteins that can deform plasma membranes to the degree required (7). Clathrin-independent mechanisms are still rather poorly understood. The study in a recent issue of PNAS by Gao, Shi, and Freund (8) sought to predict the particle size range and kinetics of clathrin-independent endocytosis in a rather general and elegant …
