When Henri Georges Adam was asked in 1955 to make a monumental sculpture for the new art museum of Le Havre, he felt that its dimensions and shape had to connect the building with its maritime environment. Moreover, it had to represent an eye on a better future because the new museum and its sculpture were erected on the ruins of a bomb-shattered past. Nature, which Adam considered as the nourishing mother of all the powers of life, was another important source of inspiration. All this led, over a period of six years, to the inauguration in 1961 of “the Signal”, a twenty-ton concrete object, delicately balancing on its pedestal and fiercely exposed to the weathering conditions of the Channel (figure 1 above).

André Malraux, then minister in charge of the expansion and promotion of the French culture, interpreted “the Signal” as a symbol of the modern and thriving Fifth Republic. Others recognize it as an arrow that invites to explore the unknown, a gate to the arts or to the ocean. For seafarers the sculpture may represent a lighthouse that signals the presence of a safe haven, for more philosophical people it signals the existence of humanity with an eye on a better future. And then, of course, there are those that see nothing but a terrible waste of public money. Locally, it is known as “the eye” although some, depending on the angle of contemplation, insist that it really resembles a mollusk shell. In short, the sculpture has more than one possible meaning. “The signal” is ambiguous.

And this, as you can learn from the textbook Signal Transduction, is also true for the first messengers that circulate our body. What they signal is not encapsulated in their chemical structure, but by the anatomical context within which they operate (type of cell and its environment) and the characteristics of the receptors that sense their presence. In more sophisticated terms, the meaning of first messengers is embedded in context. A prime example in case is the first messenger acetylcholine, a neurotransmitter released by neurons. It causes excitation of skeletal muscle cells, leading to their contraction, whereas it dampens both force and rhythmicity of the heart. In both instances it interacts with muscle cells, but not with the same receptors. Skeletal muscles express the nicotinic acetylcholine receptor, a big ion channel made of five subunits (CHRNA1, -B1, -D, -E), whereas the heart muscle and pacemaker cells (the latter which are modified muscle cells with rudimentary contractile filaments) express the muscarinic receptor, a much smaller seven-membrane spanning protein (CHRM2). The signaling pathways emanating from these receptors are totally different and this explains the difference in cellular responses. In other instances cells express the same receptor but will respond differently, migrate or secrete another second messenger, because of a different set of effectors (figure 2)

Signals are essential to life and they come in a large variety. They may come from the outside, like light, sound waves, pressure or heat but may also originate from components of commensal or infectious micro-organisms. Or they are generated by the organism itself, production of first messengers, such as hormones, growth factors, cytokines, chemokines, interleukins or neurotransmitters. Of course multicellular organisms also signal fast and precisely with the generation of action potentials that travel nerve cells.

Chapter 2 of Signal Transduction provides an extensive introduction to first messenger, their receptors and how, collectively, they provide a single cell or the organism with a symbolic representation of its environment. To speak in the words of Barbara McClintock, in her Nobel lecture of December 1983, this is essential information allowing cells to respond in a “thoughtful” manner when challenged.

Dr Kramer’s 3^rd edition of Signal Transduction is a reference on cellular signaling processes that provides a historical overview of how the concept of stimulus-response coupling arose in the early twentieth century and shaped our current understanding of the action of hormones, cytokines, neurotransmitters, growth factors and adhesion molecules.

Key Features:

• In-depth insight into a subject central to cell biology and fundamental to biomedicine, including the search for novel therapeutic interventions
• Essential signaling events embedded in rich physiological and pathological contexts
• Extensive conceptual color artwork to assist with comprehension of key topics
• Special emphasis on how molecular structure determines protein function and subcellular localization
• Employment of unambiguous protein names (symbols) in agreement with leading protein- and gene databases, allowing the learner to extend his/her exploration on the web
• Click here to find out more about the dedicated website.

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About the Author

Ijsbrand Kramer (principle author) is a Professor at the University of Bordeaux, working in the European Institute of Chemistry and Biology (IECB). He holds a Bachelors and Masters degree in BioMedicine from the University of Utrecht, The Netherlands, with a one year research-excursion in the Department of Cell Biology at the University of Liverpool, UK. Most of his research centers on the theme of inflammation, starting with neutrophils and the NADPH oxidase, synovial fibroblasts and destruction of the joint and more recently podosomes formation and extracellular matrix destruction in vascular endothelium. He has been co-director of two European Programmes (Interbio and Transbio) that aimed at enhancing industrial innovation in the biomedical sector in the South West European Region (SUDOE).

References:

• Dr Kramer’s image: for book/publicity purposes, image of the author by © Maarten Kramer

• Returning to Adam’s wish to symbolize “an eye on a better future”, Aki Kaurismäki must have been inspired by “the Signal” when he chose the port city of Le Havre as the setting of his movie “Le Havre”. It depicts an enchanting representation of humanity in the context of the European immigration problem. For more information about the sculpture and the museum of modern art of Le Havre I suggest: http://www.muma-lehavre.fr/en/