From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes

Abstract

Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization–contraction–secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an ‘emergency response’ to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory–effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system.

A flagellate-to-amoeboid switch in the closest living relatives of animals

“…Moreover, cell crawling is regulated by confinement in animal cells 9–12 , choanoflagellates, chytrid fungi 39 and dictyostelid amoebozoans 44 , suggesting that the ability to respond to confinement might be an ancient feature. These prior findings, together with our observation of an amoeboid switch in choanoflagellates, suggest that the switch from a flagellate to a crawling phenotype in response to confinement was part of an ancestral stress response in the last common choanozoan ancestor 74 . The crawling behavior of the choanozoan ancestor might even have been more extensive than what we observed in modern choanoflagellates: indeed, most choanoflagellate species have secondarily lost some genes often involved in crawling motility, such as the integrin complex 75,76 and the transcription factors Brachyury 77 and Runx 1,75 .…”

Origin of animal multicellularity: precursors, causes, consequences—the choanoflagellate/sponge transition, neurogenesis and the Cambrian explosion

“…Larvae evolved phototaxis using cryptochromes [45], not rhodopsin as in eumetazoa; some respond to gravity and have behaviour of similar complexity to eumetazoan larvae with nerves. Like rhodopsin, calcium control of cell behaviour first evolved in eubacteria [46,47] not stem eukaryotes [48], which simply adapted it for the control of actomyosin that evolved in association with bacterial wall loss and the origin of phagotrophy and endomembrane system [44,49]. …”

Choanoflagellate models — Monosiga brevicollis and Salpingoeca rosetta

“…What is the function of choanoflagellate synaptic proteins and where do they localize in S. rosetta colonies? Do choanoflagellates produce action potentials [51]? It remains to be investigated if cell-cell communication is mediated by secretion of small molecules (Figure 2d) or if cells communicate via cytoplasmic bridges (Figure 2g).…”