Signal transduction molecules at the glutamatergic postsynaptic membrane.
We have applied techniques from modern molecular biology and biochemistry to unravel the complex molecular structure of the postsynaptic membrane at glutamatergic synapses in the central nervous system. We have characterized a set of new proteins that are constituents of the postsynaptic density, including PSD-95, densin-180, citron (a rho/rac effector protein), and synaptic gp130 Ras GAP (a new Ras GTPase-activating protein). The structure of PSD-95 revealed a new protein motif, the PDZ domain, that plays an important role in the assembly of signal transduction complexes at intercellular junctions. More recently, we have used new imaging tools to observe the dynamics of autophosphorylation of CaM kinase II in intact hippocampal tissue. We have been able to detect changes in the amount of autophosphorylated CaM kinase II in dendrites, individual synapses, and somas of hippocampal neurons following induction of long-term potentiation by tetanic stimulation. In addition, we have observed a specific increase in the concentration of CaM kinase II in dendrites of neurons receiving tetanic stimulation. This increase appears to be the result of dendritic synthesis of new protein. Over the next several years we will apply similar methods to study regulatory changes that occur at the molecular level in glutamatergic synapses in the CNS as the brain processes and stores new information.
Kennedy
M B
MB
Division of Biology 216-76, California Institute of Technology, Pasadena, CA 91125, USA. kennedym@cco.caltech.edu
D000818:Animals; D001921:Brain / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003712:Dendrites / Q000502:physiology; D029721:Drosophila Proteins; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D019476:Insect Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013570:Synaptic Membranes / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D012795:Sialoglycoproteins; C092747:cno protein, Drosophila; C033652:postsynaptic density proteins; D018698:Glutamic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins