Exact definition of 'convergent' and 'divergence' in cell signalling?

Question

From what I understand, we refer to 'signal convergence' as being when two different ligands/stimuli lead to the same (at least in part) responses inside a single cell. This may or may not be due to activation of the same pathway, so for example we can refer to the response of a muscle cell to adrenaline and to stimulation by the nervous system via acetylcholine as convergent because they both lead to the release of calcium. We can also refer to the activation of the phosphoinositide pathway by both activation of beta phospholipase C via a heterotrimeric Gq protein, and activation of gamma phospholipase c via the tyrosine kinase pathway, as signal convergence.

So it seems to me that 'convergence' is defined on the level of the cell with it being, in a nutshell, different stimuli resulting in the same effect regardless of at which point in some internal signalling pathway the two responses 'converge' (at least in part).

Now with divergence I am getting slightly more stuck, and I have not seen a single, clearly stated, definition. Firstly, does divergence refer only to the level of the cell, or also for the whole organism? In particular, I am thinking of cases where a single ligand has different responses in different cells, such as adrenaline leading to increased contraction in muscle cells and glycogen breakdown in the liver (I know this isn't the best example because adrenaline technically leads to glycogen breakdown in both cell types).

Perhaps instead divergence is only referred to on the level of the cell, as with convergence? So for example generally tyrosine kinase stimulation activates several different proteins, which trigger different responses: ras, gamma phospholipase C etc. Even the phospholipase C pathway produces DAG and IP3, which have different responses. But then it seems to me like practically all pathways are divergent if this is the case, because generally pathways lead to several responses inside the cell. So with the case of phospholipase C which cleases PIP2 to DAG and IP3, the DAG can regulate metabolism and transcription etc via protein kinase C and the IP3 leads to calcium ion release that causes muscle contraction. Would this be referred to as divergence?

I would greatly appreciate if someone could just state what exactly convergence and (especially) divergence refer to. I am relatively new to cellular and molecular biology.

Answer 1

In my experience those terms are primarily used intracellularly, but I wouldn't argue that it is wrong to use them more broadly, it's just that essentially everything released extracellularly is going to have some level of divergence, so it makes more sense to use a separate classification scheme (i.e., endocrine/paracrine). Between cells, the terms are also used in other contexts such as the nervous system to refer to inputs from multiple neurons synapsing on one neuron (convergence), and outputs from one neuron synapsing on many targets (divergence).

Convergence just means multiple signalling pathways converging on the same target: like multiple pathways that can activate phospholipase C.

Divergence just means that one effector, which could be a protein such as a kinase or a second messenger like IP3, has multiple targets.

You are quite likely to get both convergence and divergence within any given signalling pathway. In my opinion, this is one of the ways that biology is not taught well in schools: textbooks might make it seem like convergence and divergence are these concrete, specific classifications, but they are really just descriptive terms. Phospholipase C pathways are a great example that displays both. If you are talking from the perspective of activation of phospholipase C, you are probably talking about convergence because there are so many ways to activate phospholipase C, but at the same time, if you talk from the perspective of the G protein subunit that is activating phospholipase C, that G protein probably has other targets as well, so that's divergence. And downstream of phospholipse C you have divergent effects of DAG and IP3.