Editorial Guide

Focus Issue: Signaling Across Membranes

Science's STKE  06 Dec 2005:
Vol. 2005, Issue 313, pp. eg11
DOI: 10.1126/stke.3132005eg11


This week’s issues of Science and Science’s STKE focus on movement of molecules and information across cellular membranes. Science highlights the mechanisms by which proteins, ions, and DNA cross the membranes of eukaryotic and prokaryotic cells. STKE addresses how information is transmitted across cell membranes to allow cells to communicate with each other and to respond to signals in their environments.

This week’s issue of Science’s STKE complements the 2 December 2005 special issue of Science entitled Crossing Membranes (http://www.sciencemag.org/sciext/membranes/). Science's STKE addresses how information is transmitted across cell membranes to initiate or contribute to cell signaling processes. Indeed, not only can cells respond to soluble signals, membrane-bound signals, and immobilized signals in the extracellular matrix, but in some cases these messages from the cell's exterior are essential for survival. The Teaching Resource by Felsenfeld provides lecture materials to teach undergraduate or graduate students about how cells that are attached to the extracellular matrix at focal adhesion sites transmit information about mechanical force through integrins. Integrins at focal adhesion complexes connect the cytoskeleton to the extracellular matrix and serve as bidirectional transducers of cellular contractile information to the extracellular matrix and of extracellular mechanical force back to the cytoskeleton (see the Connections Maps by Martin et al.). Mechanotransduction is crucial for regulating bone density, and a Review in the STKE Archive by Hughes-Fulford describes the role of mechanical stress in the regulation of osteoblast proliferation. A Perspective in the STKE Archive by Groves discusses how artificial substrates that include extracellular matrix components, as well as membrane-bound ligands, can be engineered to communicate specific signals to cells.

One well-established method for transmitting extracellular information across the cell's plasma membrane is the binding of ligands to cell surface receptors, which themselves cross the membrane or interact with proteins that span the membrane to initiate intracellular signaling cascades. Joliot and Önfelt et al. describe two different mechanisms of cellular communication. Joliot highlights the ability of certain peptide sequences to mediate transfer of soluble proteins across cellular membranes. This may be a mechanism by which certain extracellular ligands for cell surface receptors, such as the fibroblast growth factor and the opioid receptor ligand dynorphin, mediate receptor-independent signaling events. Cell-permeable peptides have also been exploited in the laboratory to investigate cell signaling and Chang et al. describe methods for using these peptides in an STKE Protocol. Önfelt et al. describe how certain cells can be connected by tunneling nanotubes, which are membranous connections that link the cytosol of one cell with that of a neighboring cell some distance away. Tunneling nanotubes have been implicated in neural cell and immune cell communication, especially calcium signaling, and cellular membranous protrusions provide a potential mechanism for bacterial and viral transfer to neighboring cells and for communication of cells during development in Drosophila.

Calcium signaling regulates many cellular processes, including vesicular secretion in excitable cells, contraction of the actin and myosin cytoskeleton in muscles, and regulation of gene expression in many different cells. Cytosolic calcium concentrations are tightly controlled and, in animal cells, calcium for signaling comes from either calcium influx through calcium channels in the plasma membrane or calcium release from the endoplasmic or sarcoplasmic reticulum. Hisastune and Mikoshiba discuss the importance of STIM1 (stromal interaction molecule 1) and IP3R (inositol triphosphate receptor) clustering in stimulating calcium influx across the plasma membrane and into the endoplasmic reticulum to refill these internal calcium stores through the processes of store-operated calcium entry or receptor-operated calcium entry. See the E-Conference and associated Perspectives for more on this controversial subject.

Calcium and several other ions are important mediators of cellular signaling, and much is now known about how these small molecules are selectively transported across the plasma and internal membranes by ion channels, pumps, and exchangers. A Perspective by Schwinger and Frank from the STKE Archives describes regulation of calcium accumulation in the cardiac SR by phospholamban. In a Science Review, Gouaux and MacKinnon discuss what insights have been revealed about ion channel and pump selectivity based on x-ray crystallographic data. Structural insights into neurotransmitter transporters that also function as ion channels are the topic of the Perspective by Vandenberg and Ryan in the STKE Archive. Many additional articles in the STKE Archives that pertain to ion channel regulation, gating, and selectivity are highlighted in the Editorial Guides by Adler and Adler et al. In addition to Reviews and Perspectives highlighting the regulation of ion channels, STKE contains several Teaching Resources that can help with preparation of lectures on ion channels and their regulation (Blitzer and Diversé-Pierluissi) or illustrate ion movement (Auerbach) across the membrane. An STKE Protocol in the Archive by Zheng and Zagotta describes the patch-clamp fluorometry (PCF) technique that records simultaneously the local structural changes and the functional states of ion channels in isolated cell membranes. Because ion transport is such a fundamental mechanism involved in cell signaling, STKE contains a broad range of resources valuable for understanding and exploring this topic.

Thus, this week STKE features several mechanisms exploited by cells to respond to signals from the outside. Transmembrane proteins, such as integrins, connect the extracellular matrix to the cytoskeleton. Extracellular signaling molecules may permeate the cell membrane stimulating internal signaling events. Membranous connections represent a newly discovered method that, like a string suspended between two cans, may provide a simple but effective line of communication between connected cells. Transport of ions across cell membranes by channels is a process that regulates key cellular signaling processes and is itself subject to stringent control mechanisms. These are but a few of the mechanisms by which intracellular signaling cascades are initiated or regulated by information that cells receive from outside the plasma membrane.

Featured in This Focus Issue

Teaching Resource

  • D. P. Felsenfeld, Regulation of complexes by cytoskeletal elements: Integrins serve as force transducers linking mechanical stimuli and biochemical signals. Sci. STKE 2005, tr27 (2005). [Abstract] [Full Text] [PDF] [Slides]


  • C. Hisatsune, K. Mikoshiba, Novel compartment implicated in calcium signaling—Is it an "induced coupling domain"? Sci. STKE 2005, pe53 (2005). [Abstract] [Full Text] [PDF]

  • A. Joliot, Transduction peptides within naturally occurring proteins. Sci. STKE 2005, pe54 (2005). [Abstract] [Full Text] [PDF]

  • B. Önfelt, M. Purbhoo, S. Nedvetzki, S. Sowinski, D. M. Davis, Long-distance calls between cells using tunneling nanotubes. Sci. STKE 2005, pe55 (2005). [Abstract] [Full Text] [PDF]

Virtual Journal

  • E. Gouaux, R. MacKinnon, Principles of selective ion transport in channels and pumps. Science 310, 1461–1465 (2005). [Abstract] [Full Text] [PDF]

Related Resources


  • M. Hughes-Fulford, Signal transduction and mechanical stress. Sci. STKE 2004, re12 (2004). [Gloss] [Abstract] [Full Text] [PDF]

  • F. H. Yu, W. A. Catterall, The VGL-chanome: A protein superfamily specialized for electrical signaling and ionic homeostasis. Sci. STKE 2004, re15 (2004). [Gloss] [Abstract] [Full Text] [PDF]


  • J. T. Groves, Learning the chemical language of cell-surface interactions. Sci. STKE 2005, pe45 (2005). [Abstract] [Full Text] [PDF]

  • R. H. G. Schwinger, K. F. Frank, Calcium and the failing heart: Phospholamban, good guy or bad guy? Sci. STKE 2003, pe15 (2005). [Abstract] [Full Text] [PDF]

  • R. J. Vandenberg, R. M. Ryan, How and why are channels in transporters? Sci. STKE 2005, pe17 (2005). [Abstract] [Full Text] [PDF]

Editorial Guides

  • E. M. Adler, Focus issue: Tuning in to the ion channel. Sci. STKE 2004, eg7 (2004). [Abstract] [Full Text] [PDF]

  • E. M. Adler, N. R. Gough, L. B. Ray, Focus issue: Ion channels: Opening the gateless gate. Sci. STKE 2003, eg9 (2003). [Full Text] [PDF]


  • M. S. S. Chang, J. P. Tam, E. Sanders-Bush, Dissecting intracellular signaling pathways with membrane-permeable peptides. Sci. STKE 2000, pl1 (2000). [Abstract] [Full Text] [PDF]

  • J. Zheng, W. N. Zagotta, Patch-clamp fluorometry recording of conformational rearrangements of ion channels. Sci. STKE 2003, pl7 (2003). [Abstract] [Full Text] [PDF]

Teaching Resources

  • R. D. Blitzer, Ligand-gated ion channels. Sci. STKE 2005, tr12 (2005). [Abstract] [Full Text] [PDF] [Slides]

  • M. Diversé-Pierluissi, Regulation of ion channels by G proteins. Sci. STKE 2005, tr21 (2005). [Abstract] [Full Text] [PDF] [Slides]

  • A. Auerbach, A speculative model of AChR gating at the frog neuromuscular junction. Sci. STKE 2003, tr2 (2003). [Abstract] [Resource Details]

Connections Map

  • K. Martin, J. Slack, S. Boerner, C. Martin, J. T. Parsons, Integrin signaling pathway. Sci. STKE (Connections Map, as seen December 2005), http://stke.sciencemag.org/cgi/cm/stkecm;CMP_6880. [Canonical Pathway]


  • D. L. Gill, R. L. Patterson, E-conference: Defining calcium entry signals. Sci. STKE Forum (Forum, as seen June 2004), http://stke.sciencemag.org/cgi/forum-display/stkeforum;14?FORUM_ID=stkeforum;14 [Discussion]

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