Organization of the core structure of the postsynaptic density

doi:10.1073/pnas.0800897105

Organization of the core structure of the postsynaptic density

*Laboratory of Neurobiology and
^†Electron Microscopy Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892;
^§Laboratory of Bioengineering and Physical Science, National Institute of Biomedical Imaging and BioEngineering, National Institutes of Health, Bethesda, MD 20892; and
^‡Department of Physiology and Cell Biophysics, Columbia University, New York, NY 10032

Contributed by Thomas S. Reese, January 28, 2008 (received for review December 19, 2007)

Abstract

Much is known about the composition and function of the postsynaptic density (PSD), but less is known about its molecular organization. We use EM tomography to delineate the organization of PSDs at glutamatergic synapses in rat hippocampal cultures. The core of the PSD is dominated by vertically oriented filaments, and ImmunoGold labeling shows that PSD-95 is a component of these filaments. Vertical filaments contact two types of transmembrane structures whose sizes and positions match those of glutamate receptors and intermesh with two types of horizontally oriented filaments lying 10–20 nm from the postsynaptic membrane. The longer horizontal filaments link adjacent NMDAR-type structures, whereas the smaller filaments link both NMDA- and AMPAR-type structures. The orthogonal, interlinked scaffold of filaments at the core of the PSD provides a structural basis for understanding dynamic aspects of postsynaptic function.

Footnotes

^¶To whom correspondence should be addressed. E-mail: treese{at}mbl.edu
Author contributions: X.C., R.D.L., and T.S.R. designed research; X.C., C.W., R.A., J.A.G., R.D.L., and T.S.R. performed research; X.L. contributed new reagents/analytic tools; X.C. analyzed data; and X.C. and T.S.R. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0800897105/DC1.