Activity of the AMPA receptor regulates drebrin stabilization in dendritic spine morphogenesis

• Published in: Journal of cell science Vol. 122; no. 8; pp. 1211 - 1219
• Main Authors: Takahashi, Hideto, Yamazaki, Hiroyuki, Hanamura, Kenji, Sekino, Yuko, Shirao, Tomoaki
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 15.04.2009
• Subjects: Animals; Cells, Cultured; Dendritic Spines - drug effects; Dendritic Spines - metabolism; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Fluorescence Recovery After Photobleaching; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - growth & development; Hippocampus - metabolism; Morphogenesis; Neuropeptides - genetics; Neuropeptides - metabolism; Protein Stability; Pseudopodia - metabolism; Rats; Receptors, AMPA - drug effects; Receptors, AMPA - metabolism; Recombinant Fusion Proteins - metabolism; Synapsins - metabolism; Synaptic Membranes - drug effects; Synaptic Membranes - metabolism; Time Factors; Transfection
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.043729

Spine morphogenesis mainly occurs during development as a morphological shift from filopodia-like thin protrusions to bulbous ones. We have previously reported that synaptic clustering of the actin-binding protein drebrin in dendritic filopodia governs spine morphogenesis and synaptic PSD-95 clustering. Here, we report the activity-dependent cellular mechanisms for spine morphogenesis, in which the activity of AMPA receptors (AMPARs) regulates drebrin clustering in spines by promoting drebrin stabilization. In cultured developing hippocampal neurons, pharmacological blockade of AMPARs, but not of other glutamate receptors, suppressed postsynaptic drebrin clustering without affecting presynaptic clustering of synapsin I (synapsin-1). Conversely, the enhancement of the action of AMPARs promoted drebrin clustering in spines. When we explored drebrin dynamics by photobleaching individual spines, we found that AMPAR activity increased the fraction of stable drebrin without affecting the time constant of drebrin turnover. An increase in the fraction of stable drebrin corresponded with increased drebrin clustering. AMPAR blockade also suppressed normal morphological maturation of spines and synaptic PSD-95 clustering in spines. Together, these data suggest that AMPAR-mediated stabilization of drebrin in spines is an activity-dependent cellular mechanism for spine morphogenesis.