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The Journal of Neuroscience, August 16, 2006, 26(33):8492-8501; doi:10.1523/JNEUROSCI.2731-06.2006

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Cellular/Molecular
Tetrameric Hub Structure of Postsynaptic Scaffolding Protein Homer

Mariko Kato Hayashi, Heather M. Ames, and Yasunori Hayashi

RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Correspondence should be addressed to Dr. Yasunori Hayashi, RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue 46-4243A, Cambridge, MA 02139. Email: yhayashi{at}mit.edu

Homer is a crucial postsynaptic scaffolding protein involved in both maintenance and activity-induced plasticity of the synapse. However, its quaternary structure has yet to be determined. We conducted a series of biophysical experiments that provide the first evidence that Homer forms a tetramer via its coiled-coil domain, in which all subunits are aligned in parallel orientation. To test the importance of the tetrameric structure for functionality, we engineered dimeric and tetrameric Homer by deleting a part of coiled-coil domain or replacing it with artificially engineered dimeric or tetrameric coiled-coil domain from a yeast protein. The structure–activity relationship was determined by assaying cocluster formation with its ligand in heterologous cells, distribution in dendritic spines, and turnover rate of protein exist in dendritic spines. Our results provide the first insight into the structure of native Homer protein as a tetramer and the functional significance conferred by that structure.

Key words: Homer; metabotropic glutamate receptor; coiled-coil; quaternary structure; synapse; scaffolding protein

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Received Dec. 16, 2005; revised July 14, 2006; accepted July 16, 2006.

Correspondence should be addressed to Dr. Yasunori Hayashi, RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue 46-4243A, Cambridge, MA 02139. Email: yhayashi{at}mit.edu

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