Hippocampal protein-protein interactions in spatial memory.
Memory consolidation in mammalian brain is accompanied by widespread reorganization of synaptic contacts and dendritic structure. Understanding of the protein-protein interactions that underlie these structural changes has been hampered by the difficulty of studying protein-protein interactions produced in vivo by signaling, learning, and other physiological responses using current methodologies. Using a novel technique that separates interacting proteins from noninteracting proteins on the basis of their protein-target affinity, we identified 16 proteins for which protein-target binding is altered in vivo by spatial learning, including stathmin, complexin I, 14-3-3, and several structural proteins including F-actin capping protein, tubulin, GFAP, and actin. Interactions between complexin and its targets (p25alpha and Drac1-like protein) and the interaction between CapZ and tubulin were calcium-dependent. The preponderance of structural proteins and proteins involved in synapse formation and reorganization of growth cones among proteins undergoing memory-specific changes in protein-protein interactions suggests that synaptic structural reorganization is a predominant feature of the consolidation phase of memory.
Nelson
Thomas J
TJ
Blanche Rockefeller Neurosciences Institute, Rockville, Maryland 20850, USA. tjnelson@brni-jhu.org
Backlund
Peter S
PS
Alkon
Daniel L
DL
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D013058:Mass Spectrometry; D008568:Memory / Q000502:physiology*; D008868:Microtubule Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009448:Neurochemistry / Q000379:methods; D009473:Neuronal Plasticity / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D013028:Space Perception / Q000502:physiology*; D050777:Stathmin
D033942:Adaptor Proteins, Vesicular Transport; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D008868:Microtubule Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D050777:Stathmin; C095992:complexin I