Signaling mechanisms underlying reversible, activity-dependent dendrite formation.
Neuronal activity and neurotrophins play a central role in the formation, maintenance, and plasticity of dendritic arbors. Here, we show that neuronal activity, mediated by electrical stimulation, KCl depolarization, or cholinergic receptor activation, promotes reversible dendrite formation in sympathetic neurons and that this effect is enhanced by NGF. Activity-dependent dendrite formation is accompanied by increased association of HMW MAP2 with microtubules and increased microtubule stability. Inhibition of either CaMKII or the MEK-ERK pathway, both of which phosphorylate MAP2, inhibits dendrite formation, but inhibition of both pathways simultaneously is required for dendrites to retract. These data indicate that neuronal activity signals via CamKII and the ERKs to regulate MAP2:microtubule interactions and hence reversible dendrite stability, and to provide a mechanism whereby activity and neurotrophins converge intracellularly to dynamically regulate dendritic morphology.
Vaillant
Andrew R
AR
Center for Neuronal Survival, Brain Tumor Research Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
Zanassi
Patrizia
P
Walsh
Gregory S
GS
Aumont
Anne
A
Alonso
Angel
A
Miller
Freda D
FD
D000320:Adrenergic Fibers / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D046508:Culture Techniques; D003712:Dendrites / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D011950:Receptors, Cholinergic; D011189:Potassium Chloride; D020932:Nerve Growth Factor; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases