High impact information on SYT2

• Synaptotagmin II negatively regulates Ca2+-triggered exocytosis of lysosomes in mast cells [1].
• Membrane topogenesis of a type I signal-anchor protein, mouse synaptotagmin II, on the endoplasmic reticulum [2].
• Synaptotagmin II mutated in both C2 domains (Delta180-183/K327,328,332Q) induced greater inhibition than mutant Delta180-183, suggesting a discrete requirement for the second C2 domain [3].
• Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II [4].
• A study of deletion mutants showed that about 30 amino acids of the central region of the C2B domain of mouse IP4BP/synaptotagmin II (315 IHLMQNGKRLKKKKTTVKKKTLNPYFNESFSF 346) are essential for inositol polyphosphate binding [4].

Biological context of SYT2

• We therefore suggest a role for synaptotagmin II as calcium-sensor during phagocytosis and secretion in neutrophils [5].
• Electrophysiological studies in cultured striatal neurons revealed that the synaptotagmin-2 deletion slowed the kinetics of evoked neurotransmitter release without altering the total amount of release [6].
• Viewed together, our results demonstrate that the synaptotagmin-2 deficiency causes a lethal impairment in synaptic transmission in selected synapses [6].
• In addition, mutagenesis of amino acid residues within this interface on Syt-II affects binding of BoNT/B [7].

Anatomical context of SYT2

• In this study, we show that synaptotagmin II is present in human neutrophils and may participate in phagocytic and in exocytotic processes [5].
• In fMLP-stimulated cells, synaptotagmin II translocated to the plasma membrane [5].
• Synaptotagmin II also translocated to the phagosome after complement-mediated phagocytosis in the presence of calcium [5].
• Using beta-galactosidase as a marker, we show that, consistent with previous studies, synaptotagmin-2 is widely expressed in spinal cord, brainstem, and cerebellum, but is additionally present in selected forebrain neurons, including most striatal neurons and some hypothalamic, cortical, and hippocampal neurons [6].
• In contrast, synaptotagmin-2-deficient neuromuscular junctions (NMJs) suffered from a large reduction in evoked release and changes in short-term synaptic plasticity [6].

Associations of SYT2 with chemical compounds

• Here we report the structure of a BoNT in complex with its protein receptor: the receptor-binding domain of botulinum neurotoxin serotype B (BoNT/B) bound to the luminal domain of synaptotagmin II, determined at 2.15 A resolution [8].
• Synaptotagmin II could confer Ca(2+) sensitivity to phagocytosis in human neutrophils [5].
• The binding activity of the recombinant H(C) of 111/NT to the protein receptor synaptotagmin II, in the presence of ganglioside GT1b, was 4.2-fold less than Okra/NT, consistent with the corresponding two NTs [9].

Regulatory relationships of SYT2

• This impairment, however, is less severe than that produced in forebrain neurons by deletion of synaptotagmin-1, presumably because at least in NMJs, synaptotagmin-1 is coexpressed with synaptotagmin-2, and both together mediate fast Ca2+-triggered release [6].

Other interactions of SYT2

• Under calcium-reduced conditions, neither synaptotagmin II nor LAMP-1 translocated to the phagosome [5].

Analytical, diagnostic and therapeutic context of SYT2

• In protein extracts from human neutrophils, we identified synaptotagmin II by Western blot as an 80 kDa protein [5].
• To analyze the role of Syt2 during exocytosis of RBL, the release of cathepsin D was assayed by immunoblotting [10].

References