The Calcium Toolkit


As the sequence of the the unicellular choanoflagellate Monosiga brevicollis continues to be analyzed, it is now clear this “simple” creature is loaded with all kinds of animal genes. Today, let us consider the research of Xinjiang Ca, from Duke University Medical Center. Cai’s paper is entitled “Unicellular Ca2+ Signaling ‘Toolkit’ at the Origin of Metazoa” (Mol. Biol. Evol. 25(7):1357–1361. 2008).

Cai introduces the situation as follows:

A fundamental question in evolutionary biology is to determine how animals (Metazoa) evolved from a unicellular ancestor by understanding the genetic basis of multicellularity. Many signaling pathways critical for cell–cell communications and animal development probably predated, or occurred concurrently with, the origins of animals. Among these pathways, Ca2+ signaling pathway plays a key second messenger role in regulating many cellular processes in virtually all types of animal cells including fertilization, contraction, exocytosis, transcription, apoptosis, and learning and memory.

It is striking to realize that intracellular concentrations of calcium play crucial roles in many metazoan processes. For example, it is the controlled rise in calcium concentration that triggers the release of neurotransmitters from a neuron and also triggers the contraction of muscle fibers.

Cai continues:

In order to execute distinct physiological functions, each animal cell type selectively expresses a unique set of proteins from a comprehensive Ca2+ signaling ‘toolkit’ which allows them to transduce appropriate extracellular
stimuli such as neurotransmitters, electrical signals, growth factors, and hormones into spatiotemporal Ca2+ signals. The large repertoire of animal Ca2+ signaling machinery is generally believed to arise from ancient multicellular organisms in which diverse forms of cell–cell communication became essential for development and physiology.

Yet Cai finds that this toolkit did not arise in some ancient multicellular creature, but instead likely existed in an ancient unicellular creature.

Here, we demonstrate for the first time the presence of an extensive Ca2+ signaling ‘toolkit’ in the unicellular choanoflagellate Monosiga brevicollis. Choanoflagellates possess homologues of various types of animal plasma membrane Ca2+ channels including the store-operated channel, ligand-operated channels, voltageoperated channels, second messenger-operated channels, and 5 out of 6 animal transient receptor potential channel families. Choanoflagellates also contain homologues of inositol 1,4,5-trisphosphate receptors. Furthermore, choanoflagellates master a complete set of Ca2+ removal systems including plasma membrane and sarco/endoplasmic reticulum Ca2þ ATPases and homologues of 3 animal cation/Ca2+ exchanger families. Therefore, a complex Ca2+ signaling ‘toolkit’ might have evolved before the emergence of multicellular animals.

That this single-celled organism possesses such a complex calcium signaling toolkit is striking, especially when considering the same unicellular creature possesses a complex tyrosine kinase toolkit and contains many genes used to connect cells into tissues. Certainly, this level of complexity is superfluous to unicellular life, as many protozoa can exist just fine without it all.

Cai then concludes with a thought-provoking question:

We conclude that an extensive Ca2) signaling ‘toolkit’ exists in the unicellular choanoflagellates, preceding the origins of animals (Metazoa). The current hypothesis of Ca2+ signaling acquires new dimensions in light of this novel discovery. Why does such an apparently simple unicellular organism need a complex Ca2+ signaling machinery?

And a complex tyrosine kinase circuit? And a battery of genes normally involved in forming tissues? Whatever the functions that are involved in this sophisticated unicellular creature, it is looking more and more as if the stage was set for the evolution of metazoan life.

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