Signals and the Whole Organism

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Posted: June 7, 2013 (Article 1)

“Ask not what the signal can do with the cell, but what the cell can do with the signal”.

For their June, 2013 issue the editors of Nature Reviews Molecular Cell Biology asked six leading researchers about the changes in our understanding of cell signaling during the past few decades. “Which emerging basic principles have you found most unexpected?”

Technical Background

In a biological context, signaling is the process whereby a molecule released at one place in the body or in a cell moves and interacts with one or more different molecules, which may then interact with still different molecules and so on, until some end result, such as the activation of a gene, is achieved.

For example, insulin is produced in the pancreas, passes through the blood stream, and interacts with receptor molecules in cell membranes. These in turn release molecules in the cell cytoplasm, initiating a complex cascade of molecular processes whereby finally resultant molecules enter the cell nucleus and modify various transcription factors, which in turn influence (“regulate”, as is usually said) the expression of numerous genes.

The answers are remarkable for their repeated emphasis upon the unexpected complexity, interwoven character, and context-dependence of molecular signaling in the organism. (“Signals” are given that designation because they are commonly said to carry “messages”. That is, they are an “information”-bearing means of “communication”. The terminology suggests that biologists are invoking something more or less closely akin to the meaning we recognize in human speaking and gesturing. This, however, must never be acknowledged.)

Anyway, we hear statements such as this: “Many cytokines [roughly, hormone-like signaling molecules not produced in specialized glands] turned out to be surprisingly multifunctional, often exerting opposite effects depending on the cellular context”. Or this from another respondent:

I think one of the most exciting basic principles to emerge during the past few decades is how the same core classes of molecules are used repeatedly to transmit cellular information, and that much of the specificity of this signalling is determined by the organization of these molecules, that is, in features such as their cellular localization and what complexes they are part of. This organization determines what molecules can crosstalk and the basic flow of information within the cell.

Another researcher similarly expresses surprise that what has been considered to be a relatively small number of core signaling pathways should produce such an abundance of different results. “This means that cellular context — the developmental or physiological history, together with what other signalling pathways are active — determines signalling output. I think we still have a lot to learn about how cell history and signal integration determine output”.

And, finally, there is this:

Signalling pathways turned out to function as parts of intricate signalling networks, the composition and connections of which provide context-dependent plasticity ... The state and composition of the signalling networks and, more than anything else, the genome-wide epigenetic status of a cell determine the cellular response to a signal. John F. Kennedy might have exclaimed: “Ask not what the signal can do with the cell, but what the cell can do with the signal”.

We can put a similar question at just about every level of observation: Ask not what the cell can do with the organ, but what the organ can do with the cell ...

In general, the surprise expressed in these answers reflects the unexpected necessity to abandon an older, strictly machine-like view of signaling pathways. Those pathways were predictable in behavior more or less like a series of connected gears and levers. The new understanding — in tune with what researchers are now glimpsing in every field of molecular biology — reflects the characteristics of life rather than mechanism. In the story of the organism’s life, causation is continually caught up in, or subordinated to, the meaning of the currently active context.

Tags: holism/contextual; signaling/contextual

Source: Hynes, Nancy E., Philip W. Ingham, Wendell A. Lim et al. (2013a). “Signalling Change: Signal Transduction through the Decades”, Nature Reviews Molecular Cell Biology vol. 14 (June), pp. 393-8. doi:10.1038/nrm3581

Further information: There is a short, readable description of some of the complexities of signaling pathways in my article, “The Unbearable Wholeness of Being”: http://BiologyWorthyofLife/mqual/genome_5.htm#signal_crosstalk

This document: https://bwo.life/comm/org/ar/2013/signals-and-whole-organism_1.htm

Steve Talbott :: Signals and the Whole Organism