Opposing roles in neurite growth control by two seven-pass transmembrane cadherins.
The growth of neurites (axon and dendrite) should be appropriately regulated by their interactions in the development of nervous systems where a myriad of neurons and their neurites are tightly packed. We show here that mammalian seven-pass transmembrane cadherins Celsr2 and Celsr3 are activated by their homophilic interactions and regulate neurite growth in an opposing manner. Both gene-silencing and coculture assay with rat neuron cultures showed that Celsr2 enhanced neurite growth, whereas Celsr3 suppressed it, and that their opposite functions were most likely the result of a difference of a single amino acid residue in the transmembrane domain. Together with calcium imaging and pharmacological analyses, our results suggest that Celsr2 and Celsr3 fulfill their functions through second messengers, and that differences in the activities of the homologs results in opposite effects in neurite growth regulation.
Shima
Yasuyuki
Y
Graduate School of Biostudies, Yoshida Konoecho, Kyoto University, Kyoto, Kyoto 606-8501, Japan.
Kawaguchi
Shin-ya
SY
Kosaka
Kazuyoshi
K
Nakayama
Manabu
M
Hoshino
Mikio
M
Nabeshima
Yoichi
Y
Hirano
Tomoo
T
Uemura
Tadashi
T
D000818:Animals; D015820:Cadherins / Q000145:classification / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D049108:Cell Enlargement / Q000187:drug effects; D002461:Cell Line, Transformed; D003001:Cloning, Molecular / Q000379:methods; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D014162:Transfection
D015820:Cadherins; C524075:Celsr2 protein, rat; C524076:Celsr3 protein, rat; D017077:Culture Media, Conditioned; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D002118:Calcium