Na,K-ATPase signal transduction triggers CREB activation and dendritic growth.
Dendritic growth is pivotal in the neurogenesis of cortical neurons. The sodium pump, or Na,K-ATPase, is an evolutionarily conserved protein that, in addition to its central role in establishing the electrochemical gradient, has recently been reported to function as a receptor and signaling mediator. Although a large body of evidence points toward a dual function for the Na,K-ATPase, few biological implications of this signaling pathway have been described. Here we report that Na,K-ATPase signal transduction triggers dendritic growth as well as a transcriptional program dependent on cAMP response element binding protein (CREB) and cAMP response element (CRE)-mediated gene expression, primarily regulated via Ca(2+)/calmodulin-dependent protein (CaM) kinases. The signaling cascade mediating dendritic arbor growth also involves intracellular Ca(2+) oscillations and sustained phosphorylation of mitogen-activated protein (MAP) kinases. Thus, our results suggest a novel role for the Na,K-ATPase as a modulator of dendritic growth in developing neurons.
Desfrere
Luc
L
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Karlsson
Marie
M
Hiyoshi
Hiromi
H
Malmersjö
Seth
S
Nanou
Evanthia
E
Estrada
Manuel
M
Miyakawa
Ayako
A
Lagercrantz
Hugo
H
El Manira
Abdeljabbar
A
Lal
Mark
M
Uhlén
Per
P
D000818:Animals; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D004563:Electrochemistry / Q000379:methods; D008564:Membrane Potentials; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D000254:Sodium-Potassium-Exchanging ATPase