Function of Drosophila Synaptotagmins in membrane trafficking at synapses

• Published in: Cellular and molecular life sciences : CMLS Vol. 78; no. 9; pp. 4335 - 4364
• Main Authors: Quiñones-Frías, Mónica C., Littleton, J. Troy
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.05.2021; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Calcium; Calcium ions; Cell Biology; Compartments; Dense core vesicles; Drosophila; Exosomes; Fruit flies; Insects; Invertebrates; Isoforms; Life Sciences; Lipids; Membrane trafficking; Membranes; Mutation; Nerve endings; Nervous system; Organelles; Peripheral nervous system; Proteins; Review; SNAP receptors; Synapses; Synaptic vesicles; Synaptotagmin; Terminals; Vesicle fusion; Vesicles; Synaptic vesicle; Synapse; Neurotransmitter release; Synaptotagmin; Exocytosis; Drosophila
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-021-03788-9

The Synaptotagmin (SYT) family of proteins play key roles in regulating membrane trafficking at neuronal synapses. Using both Ca 2+ -dependent and Ca 2+ -independent interactions, several SYT isoforms participate in synchronous and asynchronous fusion of synaptic vesicles (SVs) while preventing spontaneous release that occurs in the absence of stimulation. Changes in the function or abundance of the SYT1 and SYT7 isoforms alter the number and route by which SVs fuse at nerve terminals. Several SYT family members also regulate trafficking of other subcellular organelles at synapses, including dense core vesicles (DCV), exosomes, and postsynaptic vesicles. Although SYTs are linked to trafficking of multiple classes of synaptic membrane compartments, how and when they interact with lipids, the SNARE machinery and other release effectors are still being elucidated. Given mutations in the SYT family cause disorders in both the central and peripheral nervous system in humans, ongoing efforts are defining how these proteins regulate vesicle trafficking within distinct neuronal compartments. Here, we review the Drosophila SYT family and examine their role in synaptic communication. Studies in this invertebrate model have revealed key similarities and several differences with the predicted activity of their mammalian counterparts. In addition, we highlight the remaining areas of uncertainty in the field and describe outstanding questions on how the SYT family regulates membrane trafficking at nerve terminals.