Dataset Information

Contactin 4, -5 and -6 differentially regulate neuritogenesis while they display identical PTPRG binding sites.

ABSTRACT: The neural cell-adhesion molecules contactin 4, contactin 5 and contactin 6 are involved in brain development, and disruptions in contactin genes may confer increased risk for autism spectrum disorders (ASD). We describe a co-culture of rat cortical neurons and HEK293 cells overexpressing and delivering the secreted forms of rat contactin 4-6. We quantified their effects on the length and branching of neurites. Contactin 4-6 effects were different depending on the contactin member and duration of co-culture. At 4 days in culture, contactin 4 and -6 increased the length of neurites, while contactin 5 increased the number of roots. Up to 8 days in culture, contactin 6 progressively increased the length of neurites while contactin 5 was more efficient on neurite branching. We studied the molecular sites of interaction between human contactin 4, -5 or -6 and the human Protein Tyrosine Phosphatase Receptor Gamma (PTPRG), a contactin partner, by modeling their 3D structures. As compared to contactin 4, we observed differences in the Ig2 and Ig3 domains of contactin 5 and -6 with the appearance of an omega loop that could adopt three distinct conformations. However, interactive residues between human contactin 4-6 and PTPRG were strictly conserved. We did not observe any differences in PTPRG binding on contactin 5 and -6 either. Our data suggest that the differential contactin effects on neurite outgrowth do not result from distinct interactions with PTPRG. A better understanding of the contactin cellular properties should help elucidate their roles in ASD.

SUBMITTER: Mercati O

PROVIDER: S-EPMC3603414 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Contactin 4, -5 and -6 differentially regulate neuritogenesis while they display identical PTPRG binding sites.

Mercati Oriane O Danckaert Anne A André-Leroux Gwénaëlle G Bellinzoni Marco M Gouder Laura L Watanabe Kazutada K Shimoda Yasushi Y Grailhe Régis R De Chaumont Fabrice F Bourgeron Thomas T Cloëz-Tayarani Isabelle I

Biology open 20130110 3

The neural cell-adhesion molecules contactin 4, contactin 5 and contactin 6 are involved in brain development, and disruptions in contactin genes may confer increased risk for autism spectrum disorders (ASD). We describe a co-culture of rat cortical neurons and HEK293 cells overexpressing and delivering the secreted forms of rat contactin 4-6. We quantified their effects on the length and branching of neurites. Contactin 4-6 effects were different depending on the contactin member and duration o ...[more]

PMID: 23519440

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Dataset Information

Contactin 4, -5 and -6 differentially regulate neuritogenesis while they display identical PTPRG binding sites.

Publications

Contactin 4, -5 and -6 differentially regulate neuritogenesis while they display identical PTPRG binding sites.

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