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

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

Biology open (2013-03-23)
Oriane Mercati, Anne Danckaert, Gwénaëlle André-Leroux, Marco Bellinzoni, Laura Gouder, Kazutada Watanabe, Yasushi Shimoda, Régis Grailhe, Fabrice De Chaumont, Thomas Bourgeron, Isabelle Cloëz-Tayarani
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.

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Sigma-Aldrich
Poly-L-lysine hydrobromide, mol wt 70,000-150,000, lyophilized powder, γ-irradiated, BioXtra, suitable for cell culture