Neurite outgrowth stimulated by L1 requires calcium influx into neurons but is not associated with changes in steady state levels of calcium in growth cones.
L1, NCAM and N-cadherin are cell adhesion molecules (CAMs), present on neuronal growth cones, which promote cell-contact dependent axonal growth by activating a second messenger pathway in neurons that requires calcium influx through L- and N-type calcium channels. In the present study we show that two of these CAMs, (L1 and N-cadherin) can stimulate neurite regeneration from axotomised adult dorsal root ganglion (DRG) neurons cultured in vitro and that this response can be fully inhibited by agents that block or negate the effect of calcium influx into the neurons. However although the response required calcium influx into neurons, it was not associated with an increase in the steady state levels of calcium in neuronal growth cones. These results suggest that small localised changes, or increases in the rate of calcium cycling, in growth cones and/or filopodia, are more important for regulating axonal growth than changes in the steady-state level of calcium.
Dept. Experimental Pathology, UMDS, Guys Hospital, London.
S J
SJ
Harper
S R
SR
Bolsover
F S
FS
Walsh
P
P
Doherty
D016475:3T3 Cells; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis / Q000502:physiology*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000502:physiology*; D007700:Kinetics; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D002118:Calcium