Introduction to special issue

Crossing the Bilayer

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Science  02 Dec 2005:
Vol. 310, Issue 5753, pp. 1451
DOI: 10.1126/science.310.5753.1451

All cells, whether bacterial, plant, or animal, are enclosed by membranes, the basic components of which are lipid bilayers. The cell membrane ultimately acts as the defining principle of what constitutes a cell and what constitutes the rest of the world. Lipid bilayers are semipermeable: Small uncharged molecules can pass more or less freely from one side of the membrane to the other, but for charged species or macromolecules, such as proteins and DNA, the lipid bilayer is a major obstacle to diffusion. However, in real life, cells need to be able to transport proteins, DNA, and ions into and out of the cell, across the lipid bilayer. In this special issue, we look at the mechanisms used by cells to allow proteins, DNA, and ions to directly traverse a biological membrane.

Wickner and Schekman (p. 1452) describe how proteins can cross, or become integrated into, specific membranes. The endoplasmic reticulum membrane in eukaryotes and the plasma membrane in bacteria contain a proteinaceous pore—the translocon—that specifically promotes the translocation and integration of a multitude of signal-sequence-bearing membrane and secretory proteins into and through the membranes. Beyond these canonical systems that use the translocon, the authors mention translocation machineries and targeting strategies involved in import into different organelles, such as the mitochondria, chloroplasts, and peroxisomes, within cells and across kingdoms. Proteins are not the only macromolecules transferred across the membrane. Chen et al. (p. 1456) describe how bacteria allow DNA to traverse their membranes during the processes of conjugation and transformation and compare and contrast the molecular machineries involved in targeting and transport.

Regulating the internal composition of the cytosol is a key process in maintaining the chemistry of life, and two of the most fundamental components are the concentration and intracellular/extracellular balance of a variety of biologically important ions, including sodium, potassium, calcium, and chloride. Gouaux and MacKinnon (p. 1461) describe how ions get across membranes via transmembrane pumps and channels and explain the chemical and structural constraints involved. They describe the importance of gating within these structures, which allows for the very high specificity of transport observed and for the establishment and maintenance of important electrochemical gradients across cell membranes.

Science's Signal Transduction Knowledge Environment (STKE, addresses how information is transmitted across cell membranes to contribute to cell signaling processes. When ions and proteins cross cell membranes, they may trigger intracellular signaling cascades. Hisatsune and Mikoshiba describe how in mammalian cells, the inositol phosphate receptor (the IP3 receptor) and the calcium sensor (STIM) redistribute and cluster in response to changes in intracellular calcium and mediate calcium influx into the endoplasmic reticulum to refill intracellular calcium stores. Joliot describes how a class of cell-penetrating peptides can allow cells to communicate with one another, and Önfelt et al. describe how nanotubular membrane connections mediate intercellular communication. The Teaching Resource by Felsenfeld provides lecture materials describing how integrins transmit information from the extracellular matrix to the cytoskeleton.

How cells generate and maintain their internal structures and integrity depends in large part on the effectiveness of the membrane in keeping the inside in and the outside out. The mechanisms used in the transfer of ions and macromolecules across the cell membrane can thus be considered one of the defining principles of life, and our understanding of these processes is fundamental to our understanding of all other aspects of cellular and organismal physiology.

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