Neuroligin 1: A splice site-specific ligand for β-neurexins

Ichtchenko, Konstantin; Hata, Yoshinobu; Nguyen, Thai; Ullrich, Bernd; Missler, Markus; Moomaw, Carolyn R.; Südhof, Thomas C.

doi:10.1016/0092-8674(95)90396-8

Cited by 649 publications

(698 citation statements)

References 24 publications

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“…They bind to presynaptic alpha and beta forms of Neurexins (Ichtchenko et al, 1995(Ichtchenko et al, , 1996Missler et al, 1998;Boucard et al, 2005) and the alternative splicing of both protein families controls their binding affinities (Boucard et al, 2005;Chih et al, 2006;Comoletti et al, 2006;Fabrichny et al, 2007;Koehnke et al, 2008a,b;Shen et al, 2008). The current data suggest that Neurexin-Neuroligin binding is governed by a complex code that is based on the type of isoforms and splice variants involved, calcium binding, and glycosylation (Sudhof, 2008).…”

Section: Introductionmentioning

confidence: 60%

“…Neuroligins are a family of synaptic type I transmembrane proteins that consist of a large extracellular portion similar to cholinesterases, a glycosylated linker sequence, a transmembrane domain, and a short C-terminal tail containing a type I PDZ-binding motif (Ichtchenko et al, 1995). Neuroligins belong to a family of molecules containing the cholinesterase-like domain, called cholinesterase-like adhesion molecules (CLAMs), which include glutactin, neurotactin, and gliotactin (Gilbert and Auld, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Neuroligin proteins have been identified in different species from invertebrates to human (Ichtchenko et al, 1995;Bolliger et al, 2001;Gilbert et al, 2001;Kwon et al, 2004;Biswas et al, 2008). The mouse genome encodes four Neuroligin family members while five different genes (NLGN1, NLGN2, NLGN3, NLGN4X, and NLGN4Y) are present in the human genome (Ichtchenko et al, 1996;Bolliger et al, 2001Bolliger et al, , 2008Paraoanu et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The mouse genome encodes four Neuroligin family members while five different genes (NLGN1, NLGN2, NLGN3, NLGN4X, and NLGN4Y) are present in the human genome (Ichtchenko et al, 1996;Bolliger et al, 2001Bolliger et al, , 2008Paraoanu et al, 2006). The extracellular portion of mammalian Neuroligins contains two conserved regions subjected to alternative splicing events, indicated as Site A and B (Ichtchenko et al, 1995(Ichtchenko et al, , 1996Bolliger et al, 2001;Paraoanu et al, 2006). Usually, Neuroligin 1 and Neuroligin 3 can present three different isoforms at site A: without inserts, with insert A1/A2, or with inserts A1þA2.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the neuroligin gene family expression and evolution in zebrafish

Rissone¹,

Sangiorgio²,

Monopoli³

et al. 2010

Developmental Dynamics

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Neuroligins constitute a family of transmembrane proteins localized at the postsynaptic side of both excitatory and inhibitory synapses of the central nervous system. They are involved in synaptic function and maturation and recent studies have linked mutations in specific human Neuroligins to mental retardation and autism. We isolated the human Neuroligin homologs in Danio rerio. Next, we studied their gene structures and we reconstructed the evolution of the Neuroligin genes across vertebrate phyla. Using reverse-transcriptase polymerase chain reaction, we analyzed the expression and alternative splicing pattern of each gene during zebrafish embryonic development and in different adult organs. By in situ hybridization, we analyzed the temporal and spatial expression pattern during embryonic development and larval stages and we found that zebrafish Neuroligins are expressed throughout the nervous system. Globally, our results indicate that, during evolution, specific subfunctionalization events occurred within paralogous members of this gene family in zebrafish. Developmental Dynamics 239:688-702,

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Section: Introductionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of the neuroligin gene family expression and evolution in zebrafish

Rissone¹,

Sangiorgio²,

Monopoli³

et al. 2010

Developmental Dynamics

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“…Of the three alternative spice sites harbored in the complex, the sites A and site B inserts of NL1 have been shown to reduce NL1-NX1β binding by 2-5 fold 20 , whereas the SS#4 insert in neurexins nearly blocks the neuroligin-neurexin association 26,27 . Our structure indicates that site A of NL1 is more than 25Å from the edge of the NL1-NX1β interface, and is therefore unlikely to interfere with the neuroligin-neurexin association (Fig.…”

Section: Effects Of Splice Sites On Nl1-nx1β Interactionmentioning

confidence: 99%

Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions

Chen

Liu

Shim

et al. 2007

Nat Struct Mol Biol

147

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The heterophilic synaptic adhesion molecules, neuroligins and neurexins, are essential for establishing and maintaining neuronal circuits by modulating the formation and maturation of synapses. The neuroligin-neurexin adhesion is Ca 2+ -dependent and regulated by alternative splicing. We report a 2.4Å structure of the complex between the mouse neuroligin-1 (NL1) cholinesterase-like domain and the mouse neurexin 1β (NX1β) LNS (laminins, neurexins, and sex hormone-binding globulin-like) domain. The structure reveals a delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca 2+ -mediated, and solvent-supplemented interface, rendering it capable of being modulated by alternative splicing and other regulatory factors. Thermodynamic data support a mechanism where splicing site B of NL1 acts by modulating a salt bridge at the edge of the NL1-NX1β interface. Mapping neuroligin mutations implicated in autism indicates most such mutations are structurally destabilizing, supporting deficient neuroligin biosynthesis and processing as a common cause for this brain disorder.

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Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function

et al. 1997

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The human MUC1 gene expresses at least 2 type 1 membrane proteins: MUC1/REP, a polymorphic high m.w. MUC1 glycoprotein often highly expressed in breast cancer tissues and containing a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein, which lacks this repeat array and, therefore, is not polymorphic. Despite their documented importance in signal transduction processes, the relative expression of the 2 isoforms in epithelial tumors is unknown. Using antibody reagents which recognize different MUC1 domains, the expression of these isoforms in malig The MUC1 gene is frequently expressed with high intensity in human carcinomas, especially in breast cancer tissue (Ceriani et al., 1977;Burchell et al., 1987). In these patients, augmented concentrations of MUC1 proteins (previously referred to as episialin, H23Ag; ETA, epithelial tumor antigen; PEM, polymorphic epithelial mucin; EMA, epithelial membrane antigen; CA15-3; MCA, mammary carcinoma antigen) may be one of the earliest signs of disease progression, and, as such, the MUC1 gene has aroused much interest. A major MUC1 gene product (designated MUC1/ REP) is a polymorphic type 1 transmembrane molecule which consists of a large, heavily glycosylated extracellular domain, a transmembrane domain and a 72 amino acid cytoplasmic tail Hareuveni et al., 1990;Ligtenberg et al., 1990;Gendler et al., 1990). This isoform is proteolytically cleaved early after translation (Ligtenberg et al., 1992a) and is shed from the cell by an unknown mechanism. The MUC1 isoform, MUC1/Y, generated by alternative splicing (Zrihan-Licht et al., 1994b), has a molecular mass of 42-45 kDa and, in contrast to MUC1/REP, does not undergo proteolytic cleavage (Zrihan-Licht et al., 1994b). Furthermore, this novel MUC1 isoform retains the N-terminal as well as the transmembrane and cytoplasmic MUC1 domains but lacks the tandem repeat array that has been considered the hallmark of MUC1.To date, the relative extent of expression in epithelial tumors of the MUC1 protein containing the tandem repeat array vs. that of the novel isoform devoid of the tandem repeats has not been studied. To address this issue, we determined the expression of MUC1 gene products in epithelial tumors using not only a panel of antibodies directed against the 20 amino acid tandem repeat motif but also antibodies which specifically recognize the MUC1/Y cytoplasmic and extracellular domains. Reverse transcriptase PCR (RT-PCR) was used to assess the expression of MUC1 isoforms devoid of the tandem repeat array. Our studies demonstrate that the MUC1 isoforms lacking the tandem repeat array not only are extensively expressed in epithelial tumors but in certain cases they are almost the only MUC1 protein products observed.Significantly, the tyrosine and, to a lesser extent, the serine residues of the cytoplasmic domains of the MUC1 proteins undergo phosphorylation (Zrihan-Licht et al., 1994a). One study confirmed the phosphorylation of the MUC1 tyrosine residues (Pandey et al., 1995) and demonstrated in vivo ...

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Neuroligin 1: A splice site-specific ligand for β-neurexins

Cited by 649 publications

References 24 publications

Characterization of the neuroligin gene family expression and evolution in zebrafish

Characterization of the neuroligin gene family expression and evolution in zebrafish

Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions

Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function

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