Yuen Yan Wong (MSc student)

Yuen Yan Wong's 1st first-authored paper

Yuen Yan Wong, MSc student, and Thomas Piekut, undergrad student, both from Senatore Lab, co-authored "Early metazoan origin and multiple losses of a novel clade of RIM pre-synaptic calcium channel scaffolding protein homologues", published in Genome Biology and Evolution.

https://doi.org/10.1093/gbe/evaa097

The regulated release of neurotransmitters at the pre-synaptic terminal requires a precise arrangement of several key proteins. This includes voltage-gated calcium channels (CaV2-type), whose Ca2+ influx drives the fusion of vesicles with the cell membrane. Much of our knowledge about pre-synaptic proteins comes from studies in fruit flies, nematode worms, and rodents. Nonetheless, our understanding of the phylogeny of the synapse, and of the evolutionary history of pre-synaptic protein function, is incomplete. Rab3 Interacting Molecule, or RIM, is a particularly important organizer of the pre-synaptic terminal. In both vertebrates and invertebrates, RIM directly binds CaV2 calcium channels and brings them close to synaptic vesicles, and genetic disruption of RIM leads to severe impairments of synaptic transmission. In the recently published study from the Senatore lab, Piekut et al. conducted a phylogenomic study of RIM and CaV2 channels, finding that this key protein interaction likely emerged over 500 million years ago, in the common ancestor of bilaterians (animals with bilateral symmetry, including chordates), and cnidarians (i.e.  jellyfish, sea anemones and corals). Instead, the more early-diverging animal Trichoplax adhaerens, which lacks a nervous system and synapses, bears CaV2 channel and RIM genes but the corresponding proteins lack the motifs required for them to interact. A particularly interesting finding was the discovery of a previously unknown clade of RIM proteins in animals, that bear the same overall structure as known synaptic RIMs, but show some notable differences including at regions required for the RIM-CaV2 interaction. This novel clade of RIM proteins, whose function is completely unknown, originated near the stem lineage of animals and was selectively lost in some lineages. Interestingly, the comb-jellies, jellyfish-like creatures that are the most early-diverging animals with nervous systems and synapses, are proposed to have evolved the nervous system independently. Comb jellies are unique among animals with synapses in that they lack the canonical synaptic RIM, having only the novel RIM homologue identified in this study. Altogether, the work provides some important perspectives into the evolution of the pre-synaptic apparatus, including the functional coupling of CaV2 voltage-gated calcium channels with the pre-synaptic exocytosis machinery.

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