75% of cell plasma membrane reversibly endocytosed

In three papers in the January and February issues of the Journal of General Physiology (JGP), Don Hilgemann and colleagues have extensively characterized a previously unidentified process by which up to 75% of the cell plasma membrane can be reversibly endocytosed. This massive endocytosis ("MEND") can be elicited in a variety of cell types with a range of different experimental manipulations, including internal calcium transients in the presence of ATP, membrane treatment with sphingomyelinase, and introduction of various amphiphiles into the membrane bilayer. MEND does not employ the canonical endocytic mechanisms involving clathrin, the actin cytoskeleton or dynamins. MEND preferentially causes endocytosis of the low-ordered, cholesterol-containing membrane fraction. The mechanisms underlying MEND likely include the merger of nanoscopic low-ordered domains into larger domains with attendant changes in lipid line tension. Application of MEND promises to serve as a valuable tool in determining which membrane proteins are associated with low- or high-ordered membrane fractions.