Journal
NEURON
Volume 57, Issue 1, Pages 94-107Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2007.11.016
Keywords
-
Categories
Funding
- NIDDK NIH HHS [T32 DK007680-17, T32 DK007680, DK007680] Funding Source: Medline
- NIGMS NIH HHS [R37 GM048231, GM48231, R01 GM041292-20, R01 GM048231-12, R01 GM048231, R01 GM041292] Funding Source: Medline
- NINDS NIH HHS [R01 NS027037-18, NS027037, R01 NS027037] Funding Source: Medline
Ask authors/readers for more resources
Neuronal activity augments maturation of mushroom-shaped spines to form excitatory synapses, thereby strengthening synaptic transmission. We have delineated a Ca2+-signaling pathway downstream of the NMDA receptor that stimulates calmodulin-dependent kinase kinase (CaMKK) and CaMKI to promote formation of spines and synapses in hippocampal neurons. CaMKK and CaMKI form a multiprotein signaling complex with the guanine nucleotide exchange factor (GEF) beta PIX and GIT1 that is localized in spines. CaMKI-mediated phosphorylation of Ser516 in beta PIX enhances its GEF activity, resulting in activation of Rac1, an established enhancer of spinogenesis. Suppression of CaMKK or CaMKI by pharmacological inhibitors, dominant-negative (dn) constructs and siRNAs, as well as expression of the beta PIX Ser516Ala mutant, decreases spine formation and mEPSC frequency. Constitutively-active Pak1, a downstream effector of Rac1, rescues spine inhibition by dnCaMKI or beta PIX S516A. This activity-dependent signaling pathway can promote synapse formation during neuronal development and in structural plasticity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available