Non-Random Patterns of Membrane Proteins and Their Roles in Transmembrane Signaling

Abstract

The plasma membrane is the first line of encounter with any “own” or “foreign” molecule or hostile “visitor”. Our knowledge of the structure and function of the plasma membrane of mammalian cells was greatly advanced by the famous experiment of Frye and Edidin in 1970, which showed that distinct molecular elements of the surface of mouse and human lymphocytes labeled by green and red fluorescent dyes, respectively, were mixed upon fusing the two cell types. This finding was instrumental in the construction of the Singer–Nicolson fluid mosaic membrane model in 1972, which suggested the free mobility of proteins and other macromolecules in the plasma membrane (Singer and Nicolson 1972). Experimental observations over past decades have led to the “membrane microdomain” concept describing compartmentalization/organization of membrane components into non-random, well-defined patterns. According to recent knowledge, the lateral order of membrane lipids and proteins is a general phenomenon that may have fundamental importance in the function of individual molecules as well as in that of the whole plasma membrane (Edidin 1993, 2001; Vereb et al. 2003). The primary target of external stimuli is the plasma membrane, and nonrandom co-distribution of membrane proteins plays an important role in signal transduction across the cell membrane. The generalized occurrence of such cell-surface patterns of membrane proteins was suggested at the beginning of the 1980s (Damjanovich et al. 1981). Signal transduction processes are often accompanied by dynamic rearrangement of the two-dimensional patterns of the macromolecular constituents at the cell surface (Damjanovich et al. 1992). The structured, and at the same time dynamic, nature of the plasma membrane, i.e., the organization of its components into structures existing at different time and size scales, allows accumulation of the relevant molecules (and exclusion of others) needed for the appropriate response (Vereb et al. 1995, 2003; Edidin 2001). Protein clusters generated by the physical association/molecular proximity of the molecules (nanometer or small-scale clusters) define the basic organization level of membrane proteins (Damjanovich et al. 1998). Different types of such protein clusters can be present in the plasma membrane (Damjanovich et al. 1997b): (1) in many cases, a given “functional unit” is formed by several components/subunits (e. g., the TCR/CD3 complex; Klausner et al. 1990); (2) rearrangeNon-Random Patterns of Membrane Proteins and Their Roles in Transmembrane Signaling