The cell adhesion molecule L1 controls growth cone navigation via ankyrin(B)-dependent modulation of cyclic AMP.
During development, asymmetric Ca(2+) signals across the growth cone mediate bidirectional axon guidance depending on intracellular levels of cyclic AMP: Ca(2+) signals trigger attractive or repulsive turning when cyclic AMP levels are high or low, respectively. Here, we report that the cell adhesion molecule L1 elevates cyclic AMP levels in neurons via ankyrin(B), a protein that links the L1 cytoplasmic tail with the spectrin network. We also show that the loss of ankyrin(B) expression converts Ca(2+)-triggered attraction to repulsion when the growth cone migrates via an L1-dependent mechanism. These results indicate that ankyrin(B) regulates axon guidance via cyclic AMP.
Ooashi
Noriko
N
Laboratory for Neuronal Growth Mechanisms, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Kamiguchi
Hiroyuki
H
D000818:Animals; D000831:Animals, Newborn; D017487:Ankyrins / Q000172:deficiency / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D020439:Growth Cones / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D039842:Neural Cell Adhesion Molecule L1 / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
C498995:Ank2 protein, mouse; D017487:Ankyrins; D039842:Neural Cell Adhesion Molecule L1; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; C085112:2-nitrophenyl-EGTA; D004533:Egtazic Acid; D000242:Cyclic AMP; D002118:Calcium