Neurexins

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... 

Neurexins a protein kinase. A component of active zones that interact with RIM, syntaxin and other proteins. Cell surface proteins with more than 1,000 isoforms generated by alternative splicing from three genes. Neurexins include one of the receptors for aratrotoxin and may function in cell-cell recognition between neurons. 

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. 

Fibrinogen-like COLFI domains C. elegans neurexin IV FBG- PSI-BLAST (2) 2 X 10 4 COLFI domain of chick... 

The first a-LTX receptor to be identified was isolated from solubilized bovine brain by toxin-affinity chromatography in the presence of Ca2+ (Petrenko et al. 1990) and termed neurexin (NRX) (Ushkaryov et al. 1992) (Figure 3). 

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... 

Dudanova I, Sedej S, Ahmad M et al (2006) Important contribution of a-neurexins to Ca2+-triggered exocytosis of secretory granules. J Neurosci 26 10599-613 Fesce R, Segal JR, Ceccarelli B et al (1986) Effects of black widow spider venom and Ca2+ on quantal secretion at the frog neuromuscular junction. J Gen Physiol 88 59-81 Filippov AK, Tertishnikova SM, Alekseev AE et al (1994) Mechanism of a-latrotoxin action as revealed by patch-clamp experiments on Xenopus oocytes injected with rat brain messenger RNA. Neuroscience 61 179-89... 

Harmar AJ (2001) Family-B G-protein-coupled receptors. Genome Biol 2 3013.1-3013.10 Hata Y, Butz S, Stidhof TC (1996) CASK a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J Neurosci 16 2488-94... 

Hlubek MD, Stuenkel EL, Krasnoperov VG et al (2000) Calcium-independent receptor for a-latrotoxin and neurexin la facilitate toxin-induced channel formation evidence that channel formation results from tethering of toxin to membrane. Mol Pharmacol 57 519-28 Hurlbut WP, Ceccarelli B (1979) Use of black widow spider venom to study the release of neurotransmitters. Adv Cytopharmacol 3 87-115 87-115 Hurlbut WP, Chieregatti E, Valtorta F et al (1994) a-Latrotoxin channels in neuroblastoma cells. JMembr Biol 138 91-102... 

Ichtchenko K, Hata Y, Nguyen T et al (1995) Neuroligin 1 a splice site-specific ligand for (5-neurexins. Cell 81 435-43... 

Krasnoperov VG, Beavis R, Chepumy OG et al (1996) The calcium-independent receptor of a-latrotoxin is not a neurexin. Biochem Biophys Res Commun 227 868-75 Krasnoperov VG, Bittner MA, Beavis R et al (1997) a-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 18 925-37 Krasnoperov VG, Bittner MA, Mo W et al (2002b) Protein tyrosine phosphatase-G is a novel member of the functional family of a-latrotoxin receptors. J Biol Chem 277 35887-95 Kreienkamp HJ, Zitzer H, Gundelfinger ED et al (2000) The calcium-independent receptor for a-latrotoxin from human and rodent brains interacts with members of the ProSAP/SSTRIP/Shank family of multidomain proteins. J Biol Chem 275 32387-90 Lajus S, Lang J (2006) Splice variant 3, but not 2 of receptor protein-tyrosine phosphatase a can mediate stimulation of insulin-secretion by a-latrotoxin. J Cell Biochem 98 1552-9 Lajus S, Vacher P, Huber D et al (2006) a-Latrotoxin induces exocytosis by inhibition of voltage-dependent K+ channels and by stimulation of L-type Ca2+ channels via latrophilin in [5-cells. J Biol Chem 281 5522-31... 

Missler M, Fernandez-Chacon R, Siidhof TC (1998a) The making of neurexins. J Neurochem 71 1339-47... 

Sugita S, Ichtchenko K, Khvotchev M et al (1998) a-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors. G-protein coupling not required for triggering exocytosis. J Biol Chem 273 32715-24 Sugita S, Khvochtev M, Sfldhof TC (1999) Neurexins are functional a-latrotoxin receptors. Neuron 22 489-96... 

Thompson KM, Uetani N, Manitt C et al (2003) Receptor protein tyrosine phosphatase sigma inhibits axonal regeneration and the rate of axon extension. Mol Cell Neurosci 23 681-92 Tobaben S, Sfldhof TC, Stahl B (2002) Genetic analysis of a-latrotoxin receptors reveals functional interdependence of CIRL/latrophilin 1 and neurexin la. J Biol Chem 277 6359-65 Tobaben S, Sfldhof TC, Stahl B (2000) The G protein-coupled receptor CL1 interacts directly with proteins of the Shank family. J Biol Chem 275 36204-10 Tonks NK (2006) Protein tyrosine phosphatases from genes, to function, to disease. Nat Rev Mol Cell Biol 7 833 16... 

Ullrich B, Ushkaryov YA, Siidhof TC (1995) Cartography of neurexins more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons. Neuron 14 497-507... 

Umbach JA, Grasso A, Zurcher SD et al (1998) Electrical and optical monitoring of a-latrotoxin action at Drosophila neuromuscular junctions. Neuroscience 87 913-24 Ushkaryov YA, Hata Y, Ichtchenko K et al (1994) Conserved domain structure of (i-neurexins. Unusual cleaved signal sequences in receptor-like neuronal cell-surface proteins. J Biol Chem 269 11987-92... 

Volynski KE, Capogna M, Ashton AC et al (2003) Mutant a-latrotoxin (LTXN4C) does not form pores and causes secretion by receptor stimulation. This action does not require neurexins. J Biol Chem 278 31058-66... 

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... 

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