Abstract

""""""""The post synaptic density (PSD) at excitatory glutamatergic synapses is a complex molecular machine which appears to be a key site of information storage. New methods to probe its structure show that a lattice-like backbone labeling for PSD-95 forms its core, while other structural components-synGAP, certain spectrin isoforms, SHANK, and the kinase CaMKII-occupy various locations at the lattice (but not all components of the PSD faction localize at PSDs). The total mass of the PSD measured by electron scattering from freeze-dried PSDs is 1-2 billion Da. The PSDs in intact neurons, however, change size rapidly during activity and these changes are rapidly reversible. Immunolabeling shows that CaMKII is a major component of the added mass. Furthermore, CaMKII at the PSD is in the phosphorylated from and reversibility is inhibited by specific phosphatases, suggesting that addition of CaMKII depends on phosphorylation. Measurements of the mass of PSDs from ischemic brains shows an increase in mass sufficient to allow for the addition of up to 500 CaMKII holoenzymes. A method has been developed to purify PSDs from other components of the PSD fraction, which will allow independent measurement of CaMKII content.""""""""

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002972-04
Application #
6546848
Study Section
(LN)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
National Institute of Neurological Disorders and Stroke
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Mullasseril, Praseeda; Dosemeci, Ayse; Lisman, John E et al. (2007) A structural mechanism for maintaining the 'on-state'of the CaMKII memory switch in the post-synaptic density. J Neurochem 103:357-64
Tao-Cheng, J-H (2007) Ultrastructural localization of active zone and synaptic vesicle proteins in a preassembled multi-vesicle transport aggregate. Neuroscience 150:575-84
Tao-Cheng, Jung-Hwa; Gallant, Paul E; Brightman, Milton W et al. (2007) Structural changes at synapses after delayed perfusion fixation in different regions of the mouse brain. J Comp Neurol 501:731-40
Dosemeci, Ayse; Makusky, Anthony J; Jankowska-Stephens, Ewa et al. (2007) Composition of the synaptic PSD-95 complex. Mol Cell Proteomics 6:1749-60
Tavakoli-Nezhad, Mahboubeh; Tao-Cheng, Jung-Hwa; Weaver, David R et al. (2007) PER1-like immunoreactivity in oxytocin cells of the hamster hypothalamo-neurohypophyseal system. J Biol Rhythms 22:81-4
Chen, Xiaobing; Vinade, Lucia; Leapman, Richard D et al. (2005) Mass of the postsynaptic density and enumeration of three key molecules. Proc Natl Acad Sci U S A 102:11551-6
Tao-Cheng, J-H; Vinade, L; Winters, C A et al. (2005) Inhibition of phosphatase activity facilitates the formation and maintenance of NMDA-induced calcium/calmodulin-dependent protein kinase II clusters in hippocampal neurons. Neuroscience 130:651-6
DeGiorgis, Joseph A; Jaffe, Howard; Moreira, Jorge E et al. (2005) Phosphoproteomic analysis of synaptosomes from human cerebral cortex. J Proteome Res 4:306-15
Otmakhov, Nikolai; Tao-Cheng, Jung-Hwa; Carpenter, Stephen et al. (2004) Persistent accumulation of calcium/calmodulin-dependent protein kinase II in dendritic spines after induction of NMDA receptor-dependent chemical long-term potentiation. J Neurosci 24:9324-31
Jaffe, H; Vinade, L; Dosemeci, A (2004) Identification of novel phosphorylation sites on postsynaptic density proteins. Biochem Biophys Res Commun 321:210-8

Showing the most recent 10 out of 16 publications