Function
Synaptotagmin (SYT) are calcium-binding proteins which are conserved from nematodes to humans. Fifteen SYTs have been identified in mammals[1]. Synaptotagmin-1 (SYT1) is a synaptic vesicle membrane protein and is a sensor which induces release in neurons upon binding of Ca+2 ions[2]. The C2A domain of SYT binds phospholipids in Ca+2-dependent manner[3]. The C2B domain of SYT promotes binding to other C2B domains and to accessory proteins. Ca+2 binding causes intramolecular association of domains C2A and C2B. The synaptic fusion apparatus includes the affinity between SYT and Syntaxin-1, This affinity increases by ca. 2 orders of magnitude upon binding of Ca+2[4].
- Synaptotagmin-2 is a Ca+2 sensor for fast neurotransmitter release in caudal brain regions[5].
- Synaptotagmin-3 is a Ca+2 sensor for fast neurotransmitter release in presynapses[6].
- Synaptotagmin-4 regulates membrane traffic in neurons[7].
- Synaptotagmin-5 is dense-core vesicle-specific controlling Ca+2-regulated secretion[8].
- Synaptotagmin-7 is a plasma membrane Ca+2 sensor in synaptic exocytosis[9].
- Synaptotagmin-13 is a Ca+2-independent regulator of endocrine cell aggression and islet formation[10].
- Synaptotagmin-like proteins (SYTL) are required in a generation of a single apical surface per cell[11].
- Synaptotagmin-like protein 4 (SYTL4) is involved in intracellular membrane trafficking.
Relevance
Synaptotagmin-4 is up-regulated by chronic depolarization and seizures. Synaptotagmin-1 is a promising biomarker to monitor dysfunction and degeneration in Alzheimer disease[12].
Structural highlights
SYT-2 structure contains the SMP (synaptotagmin-like-mitochondrial-lipid binding) domain, followed by the , spacer and C2C domains. At the cup-shaped cavity at the of SYT C2A domain there are three tightly clustered Ca+2 binding sites formed by canonical 5 aspartates[13].
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3D structures of synaptotagmin
Synaptotagmin 3D structures
