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Thomas S Reese"Stable and dynamic molecular organization of the post synaptic density"

Abstract :

The post synaptic density is a large molecular machine (109 Da) which, among many functions, stabilizes receptors at synapses.
We use electron microscopy combined with high pressure freezing and immunoEM to analyze the molecular organization of PSDs as well as changes in the organization induced by activity. It has become clear that the PSD consists of two layers. The inner core of the PSD is a scaffold extending in ~40 nm from the post synaptic membrane which is stable during induced activity. Vertical filaments containing PSD-95 and other MAGUKS in the core contact receptors in the post synaptic membrane. The core is crosslinked by horizontal filaments likely to include GKAPs. Knockdown of MAGUKS results in complete collapse of sectors of the inner core. A second layer, a pallium ~100 nm thick, adheres to the core of the PSD and purifies with it when PSDs are extracted from synaptosomes. The scaffolding in this layer appears to consist of Shanks and Homer. Upon depolarization, CaMKII, SynGAP, and Shanks accumulate in the pallium and leave upon rest, while Homer does not translocate. The CaMKII that enters the pallium upon stimulation is likely to be an active kinase, and components of the pallium may be targets–the pallium may be the ‘reaction vessel’ of the PSD.

Selected publications

Spatiotemporal maps of CaMKII in dendritic spines.Khan S, Reese TS, Rajpoot N, Shabbir A.J Comput Neurosci. 2012 Jan 5. [Epub ahead of print]

SynGAP moves out of the core of the postsynaptic density upon depolarization.Yang Y, Tao-Cheng JH, Reese TS, Dosemeci A.Neuroscience. 2011 Sep 29;192:132-9. Epub 2011 Jun 26.

Isolation and ultrastructural characterization of squid synaptic vesicles.Pekkurnaz G, Fera A, Zimmerberg-Helms J, Degiorgis JA, Bezrukov L, Blank PS, Mazar J, Reese TS, Zimmerberg J.Biol Bull. 2011 Apr;220(2):89-96.

PSD-95 is required to sustain the molecular organization of the postsynaptic density.Chen X, Nelson CD, Li X, Winters CA, Azzam R, Sousa AA, Leapman RD, Gainer H, Sheng M, Reese TS.J Neurosci. 2011 Apr 27;31(17):6329-38.

Short bio

Dr Reese received a B.A. from Harvard College and an M.D. from Columbia College of Physicians and Surgeons. After a medical internship at Boston City Hospital he came to the NIH as a Research Associate. Except for a postdoctoral Fellowship in the Department of Anatomy at Harvard Medical School in 1965, Dr. Reese has remained at the NIH where he became a Section Chief in 1970 and a Laboratory Chief in 1983. Dr Reese was elected to the National Academy of Sciences in 1987. His research is on the basic cell biology of the neuron, particularly synapses and axonal transport.