Receptors Evolution Timeline

Cross references:   Receptors in General,     Receptor Evolution,     
Ligands ,   Ion Channels,     Ligand-gated Ion Channel ,     
Transmembrane Transport Evolution,   G-Protein Coupled Receptors ,      
Transmembrane Signaling Evolution        

Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels (PubMed) 
Full length HTML and PDF available online for free. 
     This is a long, very technical article which I'll abstract extensively, with numerous comments, below. 

     "Acetylcholine receptor type ligand-gated ion channels (ART-LGIC; also known as Cys-loop receptors) are a superfamily of proteins that include the receptors for major neurotransmitters such as acetylcholine, serotonin,  glycine, GABA, glutamate and histamine, and for Zn2+ ions. They play a central role in fast synaptic signaling in animal nervous systems" 
My comment
     I'm impressed that so many different ion channels have a similar construction. 

     "Using sensitive sequence-profile searches we have identified homologs of ART-LGICs in several bacteria and a single archaeal genus, Methanosarcina." 
My comment
     So!  The ART-LGICs go all the way back to the archaea!   

     "Analysis of phyletic patterns suggests that the ART-LGICs are currently
absent in all other eukaryotic lineages except animals." 
My comment
     Perhaps the "
fast synaptic signaling", mentioned above, is the fundamental difference between we animals and "all other eukaryotic lineages". 
     See:  Eukaryotes for the impressive array of "all other eukaryotic lineages". 
However, the lack of ART-LGICs in
"all other eukaryotic lineages" is really surprising if eukaryots evolved from a prokaryote which had ART-LGICs.   

     "Contextual connections suggest that the prokaryotic forms may function as chemotactic receptors for low molecular weight solutes. The phyletic patterns and phylogenetic relationships suggest the possibility that the metazoan receptors emerged through an early lateral transfer from a prokaryotic source, before the divergence of extant metazoan lineages." 
My comment
So, what do
"all other eukaryotic lineages" use as "chemotactic receptors for low molecular weight solutes"? 

"The neuronal ligand- or neurotransmitter-gated ion channels (LGICs) combine the functionalities of a receptor and ion channel in a single protein, and mediate fast synaptic signaling." 
     "The ART-LGICs characterized to date show ion selectivity.  The excitatory channels, such as the acetylcholine and serotonin receptors, the mammalian Zn receptors ... allow the flow of cations, whereas the inhibitory receptors, such as those for glycine and GABA, ... allow the flow of anions. Cation or anion selectivity of the channel is principally governed by the charge distribution in the linker between the transmembrane helices
M1 and M2." 
My comment:  
    At this point, the article gives a long, detailed description of the operation of a
ART-LGIC.  If you're interested, click on the link. 

     "The pattern of the residues conserved in both the metazoan and bacterial receptors suggests that a common mechanism of channel-gating is 
likely to operate throughout this superfamily."


Evolutionary origin of cholinergic macromolecules ... (PubMed) 
Full length article online. 
Our results demonstrate that the record of evolutionary history for nervous system proteins can be read across the boundaries of separation between vertebrates and invertebrates. They also provide molecular evidence for the common evolutionary origins of the nervous and endocrine systems in vertebrates--both evolving to make intercellular communication possible.
My comment:      
     I'm not sure, but I think the "
common evolutionary origins", referred to above, are the "common evolutionary origins" of hormones, neuromodulators and neurotransmitters.   

Evolutionary Origins of Intercellular Communiction (PubMed) 
Abstract only online.  I have PDF. 
By extending the evolutionary age of the vertebrate hormones from the vertebrates to include the metazoans, we expand their phyletic distribution about 30-fold. By tracing these molecules into the unicellular range including both eukaryotes and prokaryotes, the distribution of these molecules becomes very wide indeed.

Evolutionary Origins of Neuropeptides, Hormones, and Receptors (PubMed)$=relatedarticles&logdbfrom=pubmed 
Abstract only online.  I have PDF. 
Materials that resemble hormonal peptides and neuropeptides, previously thought to be restricted to multicellular animals, are present in protozoa, bacteria, and higher plants. There is also evidence for substances in microbes that bind hormones and other messengers, which resemble receptors of vertebrates. Therefore, we suggest that the molecules of intercellular communication probably arose much earlier in evolution than the endocrine, nervous, and immune systems.

    "In Achlya, a unicellular water mold, male and female forms communicate via sex pheromones that are quite similar in structure to steroid hormones of vertebrates. In addition, the male (but not female) of the species contains a substance in the cytoplasm that specifically binds the pheromone released by the female. Interestingly, this binding substance physicochemically resembles very closely the steroid hormone receptors of vertebrates (1 7)." 
    "We suggest that their specific ancestor molecules arose at a relatively early stage of evolution in unicellular organisms. Later, in the course of evolution, new, highly specialized anatomic systems of multicellular organisms such as the nervous system, the endocrine system, and the immune system adopted and adapted these preexisting molecules, both the messengers and their receptors, to meet their intercellular communication needs." 

Molecular Ontogeny of Major Neurotransmitter Receptor Systems in the Mammalian Central
Nervous System: Norepinephrine, Dopamine, Serotonin, Acetylcholine, and Glycine (PubMed) 
Only abstract available online.  I got the PDF from the library.   
My comment:     
     This article in The Journal of Child Neurology is a review intended for readers who are fairly new to the field.  If you want a broad overview in fairly plain English, this is for you.  However, it doesn't break any new ground.  So if you're already familiar with the field, you'll be disappointed.  I originally accessed the article because I misunderstood what the author meant by "ontogeny".  I thought he meant change through evolution, but instead, he means change from embryo to adult.  I've copy-and-pasted part of the section on serotonin, below, because, at the moment, I'm particularly focused on serotonin.  There are similar sections on the other neurotransmitters mentioned in the title. 
from the article    
     "Serotonin binds to a large family of pre- and postsynaptic receptors; serotonin receptors are currently assigned to one of seven families (5-HTl through 5-HT7), comprising more than a dozen subtypes that can be distinguished on a structural and pharmacologic basis.   
    Based on autoradiographic studies, it is clear that each serotonin receptor sub-type has a highly distinctive pattern of distribution in the central nervous system.  By modulating neuronal activity and neurotransmitter release in a widespread manner, serotonin receptors affect behavior through many interdependent central nervous system pathways.   
    Six members of the serotonin receptor family belong to the seven transmembrane-spanning (7TM) G-protein coupled metabotropic receptors, and the seventh receptor (ie, serotonin 3) is a homopentameric ligand-gated ion channel, permeable to cations, that causes rapid depolarization of neurons.  
    In general, 5-HT, receptor subtypes are negatively coupled to adenylate cyclase via G proteins (resulting in inhibition), whereas members of the 5-HT3 family are coupled positively to phospholipase C and mobilize intracellular calcium (and are thus excitatory).’"