Role of the membrane skeleton in creation of microdomains.

Abstract

The membrane skeleton is a specialized part of the cytoskeleton that is in close proximity to the cell membrane with a protein composition and structure that differs from that of the bulk cytoskeleton. The membrane skeleton and various transmembrane proteins bound to it form a mosaic of compartments in the membrane that is responsible for the temporary confinement of membrane proteins and lipids and controls the rate of their repetitive hop movements between these membrane skeleton-based compartments, known as "hop diffusion", found by observation of single-molecule diffusion. Such hop diffusion has been found to be universal with compartment sizes that range from 30 to 700 nm, depending on the cell type. The part of the membrane skeleton that is directly involved in temporal confinement of membrane molecules has been successfully imaged by raster scanning a single membrane molecule using an optical trap (single molecule scanning optical force imaging). Such compartmentalization enables dynamic spatial regulation of signal transduction in the plasma membrane, by arresting signaling complexes of activated receptor molecules and enlarged, stabilized rafts within a compartment. Furthermore, high concentrations of the membrane skeleton and its associated immobile transmembrane proteins are involved in formation of the cell membrane polarity such as is found across the initial segment between the axon and the cell body in neurons. Argument is advanced that the creation of various membrane domains in the cell membrane must be influenced by the membrane skeleton.