Neurexins binding

Ichtchenko, K, Nguyen, T and Sudhof, TC (1996) Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem 271 2676-2682. 

Synaptotagmins Membrane proteins with at least 15 isoforms that contain C2 domains bind Ca2+ and phospholipids and interact with neurexins, AP2 and syntaxins. Synaptotagmins 1 and 2 may function as Ca2+ sensors in fast Ca2+-dependent neurotransmitter release... 

Neuroligin is a protein that binds to the PDZs of PSD95. Neuroligin reaches into the synaptic cleft and interacts with [3-neurexin, a protein that reaches into the synaptic cleft from the presynaptic side P-neurexin is anchored presynaptically to the PDZ domain of another MAGUK, CASK. This arrangement connects the pre-and postsynaptic elements and stabilizes the synapse mechanically. 

Batt J, Asa S, Fladd C et al (2002) Pituitary, pancreatic and gut neuroendocrine defects in protein tyrosine phosphatase-sigma-deficient mice. Mol Endocrinol 16 155-69 Biederer T, Siidhof TC (2000) Mints as adaptors. Direct binding to neurexins and recruitment of muncl8. J Biol Chem 275 39803-6... 

D Amour F, Becker FE, van Riper W (1936) The black widow spider. Q Rev Biol 11 123-60 Davletov BA, Krasnoperov V, Hata Y et al (1995) High affinity binding of a-latrotoxin to recombinant neurexin la. J Biol Chem 270 23903-5... 

Davletov BA, Meunier FA, Ashton AC et al (1998) Vesicle exocytosis stimulated by a-latrotoxin is mediated by latrophilin and requires both external and stored Ca2+. EMBO J 17 3909-20 Davletov BA, Shamotienko OG, Lelianova VG et al (1996) Isolation and biochemical characterization of a Ca2+-independent a-latrotoxin-binding protein. J Biol Chem 271 23239 15 Dean C, Scholl FG, Choih J et al (2003) Neurexin mediates the assembly of presynaptic terminals. Nat Neurosci 6 708-16... 

Dresbach T, Neeb A, Meyer G et al (2004) Synaptic targeting of neuroligin is independent of neurexin and SAP90/PSD95 binding. Mol Cell Neurosci 27 227-35... 

Volynski KE, Silva JP, Lelianova VG et al (2004) Latrophilin fragments behave as independent proteins that associate and signal on binding of LTXN4C. EMBO J 23 4423-33 Volynski KV, Meunier FA, Lelianova VG et al (2000) Latrophilin, neurexin and their signalling-deficient mutants facilitate a-latrotoxin insertion into membranes but are not involved in pore formation. J Biol Chem 275 41175-83... 

Neurexin-1, a trans-synaptic cell adhesion molecule that binds to neuroligins, has also been implicated in ASD (Szatmari et al., 2007 Feng et al., 2006). Briefly, large internal deletions in neurexin-1 coding exons were found in two affected siblings... 

In both cases alternative splicing not only increases the diversity but also regulates binding between neuroligins and neurexins (Fig. 2). Indeed the neurexin SS4 insert seems to modulate binding to neuroligins, whereas the neuroligin SSB insert strictly... 

Biederer, T and Sudhof, TC (2000) Mints as adaptors. Direct binding to neurexins and recruitment of muncl8. J Biol Chem 275 39803-39806. 

Boucard, AA, Chubykin, AA, Comoletti, D, Taylor, P and Sudhof, TC (2005) A splice-code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to a- and P-neurexins. Neuron 48(2) 229-236. 

Nguyen, T and Sudhof, TC (1997) Binding properties of neuroligin 1 and neurexin Ibeta reveal function as heterophiUc cell adhesion molecules. J Biol Chem 272 26032-26039. 

Shen, KC, Kuczynska, DA, Wu, IJ, Murray, BH, Sheclder, LR and Rudenko, G (2008) Regulation of neurexin Ibeta tertiary structure and ligand binding through alternative splicing. Structure 16 422-431. 

By contrast, tetanus toxin primarily has a central action it is transported in retrograde fashion up the motor neuron to its soma in the spinal cord. From there the toxin migrates to inhibitory neurons that synapse with the motor neuron and blocks exocytosis in the inhibitory neuron. The block of release of inhibitory transmitter gives rise to tetanus or spastic paralysis. The toxin from the venom of black widow spiders (a-latrotoxin) binds to neurexins, transmembrane proteins that reside on the nerve terminal membrane, resulting in massive synaptic vesicle exocytosis. 

---