Could anyone please tell me the difference between canonical and non-canonical signalling pathway.
Hi Shishir,
Here is a starting point: the Science Signaling journal have a definition here: http://stke.sciencemag.org/about/help/cm.dtl
"Canonical Pathways" -- idealized or generalized pathways that represent common properties of a particular signaling module or pathway..." they also define "specific pathways" as those specific of tissues, cell lines, etc.
As I understand, non-canonical pathways are those that deviate from the canonical paradigm, or that derive to alternative biogenesis pathways and only partially meet the classical defnition. Sometimes non-canonical pathways are those which are alternative less known pathways.
Canonical and non-canonical pathways may be semi-redundant, which means that there may be process(es) where these pathways converge.
I hope this help and that other researchers come up with more detailed definitions
Good luck!
Rolando
To add to the other comments, I think in general its the literal meaning of well established and classically characterized pathway being canonical and the alternative proposed /non-generalized or later discovered pathway as non canonical / atypical.
The terminology of canonical vs non-canonical has become less meaningful. In the classical example of the Wnt pathway, canonical refers to the pathway components that lead to stabilization of beta-catenin in response to certain Wnt ligands. Any other biological outcomes of Wnt signaling are termed non-canonical. But this is an historic accident due to the pioneering work in Drosophila genetics that initially detailed the genes associated with wingless signaling. Different Wnt ligands and Frizzled receptors can engage various signaling responses including G protein coupled receptors, calcium signals, etc. I am also not sure one can call a given response typical versus atypical - it all depends on the precise stimuli and cell type. We know that cellular context, crosstalk and multiple outputs have rendered the idea of linear pathways to the garbage bin and so its probably better to think of programs of responses than pathways. Best not to think "canonically" as a scientist!
I agree with James. We should not talk on canonical vs. non-canonical, which does not make sense in term of signaling
One question I have always been wondering is that when people mention a pathway in the literature, for instance, the Wnt pathway, what are the details in people's mind? Do they refer to the canonical pathway?
Basically, what is called canonical is largely in the eye of the beholder. As a rule, the pathway discovered first is called canonical in every field. In GPCR field signaling via G proteins is called canonical, whereas G protein-independent signaling via arrestins is called non-canonical. Recently, the signaling by GPCRs from the cell surface was called canonical, as opposed to signaling by internalized GPCRs via the same G proteins, which was called non-canonical.
Can't agree with James R. Woodgett more: there is no such thing as a pathway, cells use complex signaling networks (the interactions between branches are often called "cross-talk" by those who prefer to think in terms of linear pathways).
Very rightly said....Multidirectional cooperativity is the norm of signaling networks rather than oversimplistic canonical or non-canonical linear pathways...
Its a historical problem; for Wnt signalling, the distinction was anything that stabilized beta-catenin was canonical and everything else (i.e. inhibited beta-catenin, degraded beta-catenin or activated other signalling pathways was "non-canonical"). Now in the Wnt field "canonical" the designation is Wnt/beta-catenin. Workers using NFkB then distinguished canonical from non-canonical NFkB signalling; again the standard or first elucidated NFkB pathway was the "canonical" one, the others became 'non-canoncial".
Its jargon, so its best to have some operative distinction (like the Wnt workers now use Wnt/beta-catenin vs Wnt/JNK. Its probably best to use canonical only in quotations in the discussion too.
Wnt signaling is the best example for canonical and non-canonical pathway.But the exact difference between two Canonical followed by classic way that mean in organized process ad non-canonical refers to non-classical which mean in zig-zag way or not in order or followed by another pathway. That is why the Wnt signaling pathway is giving the best example to describe it. If you go through the two mechanisms of this you can find it that one canonical followed by systematical manner. However, non-canonical is followed two pathways which activate the Wnt in two different process one is JNK and another is Wnt/Ca+. In other words, it is saying that canonical is beta -catenin dependent and non-canonical is beta-catenin independent. Hope so this explanation would help you to clear your doubts.
Well said in all responses. In a network of signalling use of such terminology unnecessarily confuses the scientist. Better should be avoided.
Surprised to see use of such terminology in upcoming June 2017 paper, in Trends in Cell Biology, http://dx.doi.org/1016/j.tcb.2017.01.006
Canon is the fiat from church- absolute and not to be deviated upon. Canonical means the overarching, most significant and the central most belief. Rest all are non canonical
As much as I know, the canonical pathway means which signaling pathway is constitutively active (naturally occurring inside the body, cells, or tissue). Non-canonical pathway means inducible signaling pathway (might be from drug, chemicals, or xenobiotics from outside of the body).
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