synaptotagmiini

Synaptotagmiini, commonly referred to in English as synaptotagmin, is a family of calcium-sensing membrane proteins that regulate fast, calcium-triggered exocytosis in neurons and other secretory cells. They are anchored to secretory vesicles through a short transmembrane domain, and their cytosolic portions contain two calcium-binding C2 domains (C2A and C2B) that engage calcium, phospholipids, and SNARE proteins to promote membrane fusion. The resulting Ca2+-dependent triggering step couples calcium entry to neurotransmitter or hormone release.

Vertebrates express multiple synaptotagmin genes (for example SYT1, SYT2, SYT7, SYT4, SYT9, and others). The best studied are synaptotagmin-1 and synaptotagmin-2, which serve as primary sensors for fast synchronous neurotransmitter release at many central and peripheral synapses. Other family members contribute to slower or asynchronous release, secretion from dense-core vesicles, or exocytosis in non-neuronal cells, depending on cellular context and subcellular localization.

Mechanistically, binding of Ca2+ to the C2 domains triggers conformational changes that promote interaction with the SNARE complex and the plasma membrane, lowering the energy barrier to fusion. In addition to directly triggering fusion, synaptotagmins modulate vesicle docking, priming, and fusion pore dynamics, with isoform- and tissue-specific effects.

Clinical relevance: Mutations or dysregulation of synaptotagmin genes, especially SYT1, have been associated with neurodevelopmental disorders that can include motor and language delays, seizures, and autism spectrum features. Animal models reveal essential roles in synaptic transmission, plasticity, and behavior.

Evolution and distribution: The synaptotagmin family is conserved across metazoans, with gene duplications generating diverse isoforms in vertebrates and specialized roles in neuronal and secretory pathways.