Neural recognition molecule NB‐2 of the contactin/F3 subgroup in rat: Specificity in neurite outgrowth‐promoting activity and restricted expression in the brain regions

Ogawa, Jun; Lee, Sai Peck; Itoh, Kouichi; Nagata, Saburo; Machida, Takeo; Takeda, Yasuo; Watanabe, Kazutada

doi:10.1002/jnr.1133

Cited by 37 publications

(30 citation statements)

References 28 publications

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“…These similar phenotypes suggest that the physical association of PTPRG and CNTN6 may be important for acquiring proper motor functions. CNTN5 is expressed early postbirth and its expression is the strongest in regions involved in the auditory pathway, in particular in the cochlear nuclei (25,26). This localization of CNTN5 matches that of PTPRG (4), which is also found, at least at the embryonic stage, in the nuclei of the vestibulocochlear nerve responsible for carrying signals about hearing and balance.…”

Section: Discussionsupporting

confidence: 58%

The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules

Bouyain

Watkins

2010

Proc. Natl. Acad. Sci. U.S.A.

105

128

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The receptor protein tyrosine phosphatases gamma (PTPRG) and zeta (PTPRZ) are expressed primarily in the nervous system and mediate cell adhesion and signaling events during development. We report here the crystal structures of the carbonic anhydrase-like domains of PTPRZ and PTPRG and show that these domains interact directly with the second and third immunoglobulin repeats of the members of the contactin (CNTN) family of neural recognition molecules. Interestingly, these receptors exhibit distinct specificities: PTPRZ binds only to CNTN1, whereas PTPRG interacts with CNTN3, 4, 5, and 6. Furthermore, we present crystal structures of the four N-terminal immunoglobulin repeats of mouse CNTN4 both alone and in complex with the carbonic anhydrase-like domain of mouse PTPRG. In these structures, the N-terminal region of CNTN4 adopts a horseshoe-like conformation found also in CNTN2 and most likely in all CNTNs. This restrained conformation of the second and third immunoglobulin domains creates a binding site that is conserved among CNTN3, 4, 5, and 6. This site contacts a discrete region of PTPRG composed primarily of an extended β-hairpin loop found in both PTPRG and PTPRZ. Overall, these findings implicate PTPRG, PTPRZ and CNTNs as a group of receptors and ligands involved in the manifold recognition events that underlie the construction of neural networks.cell adhesion | crystal structure | Ig superfamily | receptor protein tyrosine phosphatase

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Section: Discussionsupporting

confidence: 58%

The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules

Bouyain

Watkins

2010

Proc. Natl. Acad. Sci. U.S.A.

105

128

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“…Although the p value for association, 4,09 × 10 -7 , falls short of genome-wide significance, this finding is consistent with a further possible involvement of CNTN5 in ASD. The contactin-5 protein is a neural cell recognition molecule of the contactin/F3 subgroup, which promotes neurite outgrowth of the cerebral cortical neurons in the auditory pathway, suggesting that it plays specific roles in the development and maturation of certain regions of the brain [Ogawa et al, 2001]. The contactin-5 protein also binds to the amyloid precursor-like protein 1 (APLP1), thus, possibly forming a network by physical interactions of encoded proteins [Shimoda et al, 2012].…”

Section: Discussionmentioning

confidence: 99%

A Candidate Gene Association Study Further Corroborates Involvement of Contactin Genes in Autism

Poot¹

2014

Mol Syndromol

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Although autism spectrum disorder (ASD) shows a high degree of heritability, only a few mutated genes and mostly de novo copy number variations (CNVs) with a high phenotypic impact have as yet been identified. In families with multiple ASD patients, transmitted CNVs often do not appear to cosegregate with disease. Therefore, also transmitted single nucleotide variants which escape detection if genetic analyses were limited to CNVs may contribute to disease risk. In several studies of ASD patients, CNVs covering at least one gene of the contactin gene family were found. To determine whether there is evidence for a contribution of transmitted variants in contactin genes, a cohort of 67 ASD patients and a population-based reference of 117 healthy individuals, who were not related to the ASD families, were compared. In total, 1,648 SNPs, spanning 12.1 Mb of genomic DNA, were examined. After Bonferroni correction for multiple testing, the strongest signal was found for a SNP located within the CNTN5 gene (rs6590473 [G], p = 4.09 × 10-7; OR = 3.117; 95% CI = 1.603-6.151). In the ASD cohort, a combination of risk alleles of SNPs in CNTN6 (rs9878022 [A]; OR = 3.749) and in CNTNAP2 (rs7804520 [G]; OR = 2.437) was found more frequently than would be expected under random segregation, albeit this association was not statistically significant. The latter finding is consistent with a polygenic disease model in which multiple mutagenic mechanisms, operating concomitantly, elicit the ASD phenotype. Altogether, this study corroborates the possible involvement of contactins in ASD, which has been indicated by earlier studies of CNVs.

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“…PI-PLC treatment was performed as described previously (Ogawa et al, 2001). Briefly, rat brains at postnatal day 6 (P6) were homogenized in 1 mM NaHCO 3 , pH 7.9, 0.2 mM CaCl 2 , 0.2 mM MgCl 2 , and 1 mM spermidine containing the protease inhibitors leupeptin (4.8 g/mL), pepstatin (0.7 g/mL), p-amidinophenylmethylsulfonyl fluoride hydrochloride (174 g/mL), and aprotinin (6 g/mL).…”

Section: Phosphatidyl Inositol-specific Phospholipase C (Pi-plc) Treamentioning

confidence: 99%

Impaired motor coordination in mice lacking neural recognition molecule NB‐3 of the contactin/F3 subgroup

et al. 2003

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The neural recognition molecule NB-3, which belongs to the contactin subgroup of the immunoglobulin superfamily, is expressed exclusively in the nervous system and mainly upregulated at the early postnatal stage during mouse brain development. The expression of NB-3 in the cerebellum increases until adulthood. In contrast, the expression in the cerebrum declines to a low level after postnatal day 7. To characterize the functional roles of NB-3 in vivo, we generated NB-3-deficient mice by substituting a part of the NB-3 gene with the beta-galactosidase (Lac Z) gene. Complete overlap of the Lac Z expression in the heterozygous mouse brain with the NB-3 immunostaining pattern in the rat cerebellum and with the previously reported pattern of in situ hybridization of NB-3 transcripts indicated that Lac Z expression reflects the expression of NB-3 in the mouse brain. NB-3-deficient mice were viable and fertile. The formation and organization of all nuclei and layers throughout the brains of mutant mice appeared normal. Behavioral tests to examine motor function showed that the mice deficient for NB-3 were slow to learn to stay on the rotating rod in the rotorod test during repeated trials, and that they displayed dysfunction of equilibrium and vestibular senses in the wire hang and horizontal rod-walking tests. In contrast, the mutant mice showed no difference of grasp force from the wild-type mice. Thus, NB-3-deficient mice are impaired in motor coordination.

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Neural recognition molecule NB‐2 of the contactin/F3 subgroup in rat: Specificity in neurite outgrowth‐promoting activity and restricted expression in the brain regions

Cited by 37 publications

References 28 publications

The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules

The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules

A Candidate Gene Association Study Further Corroborates Involvement of Contactin Genes in Autism

Impaired motor coordination in mice lacking neural recognition molecule NB‐3 of the contactin/F3 subgroup

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