Confusion in the nomenclature of synaptotagmins V and IX: Which is which?

Synaptotagmins (Syts) are a large family of evolutionarily conserved proteins that comprise an N-terminal single transmembrane domain and C-terminal cytoplasmic tandem C2 Ca²⁺/phospholipid-binding motifs. Fifteen distinct Syt isoforms (Syts I-XV) are present in mice and humans, and some of them, but not all, have been shown to regulate Ca²⁺-dependent vesicular exocytosis, presumably by serving as a Ca²⁺-sensor. The nomenclature of two Syt family members, Syt V and Syt IX, both of which are present on dense-core vesicles in certain endocrine cells, is very confusing in the literature, because two different Syt V sequences were reported at the same time by several groups, and each of them is often referred to as Syt IX. In this mini-review we describe the literature on the identification of Syt V and Syt IX and their role in vesicular exocytosis to clarify the confusion in Syt V/IX nomenclature.