Synaptotagmine

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The molecular mechanism that regulates exocytosis in the release of neurotransmitters .

Synaptotagmins are a group of 17 proteins located on cell membranes , which are characterized by an N-terminal transmembrane region (TMR), a variable connection and two C-terminal C2 domains (C2A and C2B). There are several C2 domain-bearing protein groups that are related to synaptotagmins, including Ferline, E-Syts, and MCTPs, as well as RIMs, Munc13s, and B / K.

function

Based on their endocrine distribution in the brain and their biochemical capabilities, synaptotagmine C2 domains bind calcium . It is therefore believed that synaptotagmins act as calcium sensors that control the release of neurotransmitters and hormones .

Although all synaptotagmins are structured very similarly, only eight (1, 2, 3, 5, 6, 7, 9, and 10) bind calcium.

Proteins from the group of synaptotagmins can be found through interaction with β-neurexin or SNAP-25 in exocytosis in the early (docking of the synaptic vesicles on the presynaptic membrane) and in the late phase.

In 2006 it was possible to show in an experiment that Synaptotagmin 1 can displace complexin from the SNARE complex in the presence of calcium . This is considered to be one of the final chemical reactions in exocytosis.

The C2 domains then control the fusion of the synaptic vesicles in the context of exocytosis.

Individual evidence

  1. ↑ Fukuda M, Moreira JE, Liu V, Sugimori M, Mikoshiba K, Llinas RR: Role of the conserved WHXL motif in the C terminus of synaptotagmin in synaptic vesicle docking . In: Proc Natl Acad Sci USA . 97, 2000, pp. 14715-14719. doi : 10.1073 / pnas.260491197 .
  2. ↑ Schiavo G, Stenbeck G, Rothman JE, Söllner TH: Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t-SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses . In: Proc Natl Acad Sci USA . 94, 1997, pp. 997-1001. doi : 10.1073 / pnas.94.3.997 .
  3. ↑ Pang ZP, Melicoff E, Padgett D, Liu Y, Teich AF, Dickey BF, et al .: Synaptotagmin-2 is essential for survival and contributes to Ca 2+ triggering of neurotransmitter release in central and neuromuscular synapses . In: The Journal of Neuroscience . 26, 2006, pp. 13493-13504. doi : 10.1523 / JNEUROSCI.3519-06.2006 .
  4. ↑ Maximov A, Südhof TC : Autonomous function of synaptotagmin 1 in triggering synchronous release independent of asynchronous release . In: Neuron . 48, 2005, pp. 547-554. doi : 10.1016 / j.neuron.2005.09.006 .
  5. ^ O'Connor V, Lee AG: Synaptic vesicle fusion and synaptotagmin: 2B or not 2B? . In: Nature Neuroscience . 5, 2002, pp. 823-824. doi : 10.1038 / nn0902-823 .
  6. ↑ Tang J, Maximov A, Shin OH, Dai H, Rizo J, Südhof TC: A complexin / synaptotagmin 1 switch controls fast synaptic vesicle exocytosis . In: Cell . 126, No. 6, 2006, pp. 1175-1187. doi : 10.1016 / j.cell.2006.08.030 .
  7. ↑ Zimmerberg J, Akimov SA, Frolov V: Synaptotagmin: fusogenic role for calcium sensor? . In: Nature Structural & Molecular Biology . 13, 2006, pp. 301-303. doi : 10.1038 / nsmb0406-301 .
  8. ↑ Fernández-Chacón R, Königstorfer A, Gerber SH, García J, Matos MF, Stevens CF, et al .: Synaptotagmin I functions as a calcium regulator of release probability . In: Nature . 410, 2001, pp. 41-49. doi : 10.1038 / 35065004 .