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Title: NMDA-induced accumulation of Shank at the postsynaptic density is mediated by CaMKII

Highlights: • NMDA-induces accumulation of Shank at the postsynaptic density. • Shank accumulation is preferential to the distal region of the postsynaptic density. • Shank accumulation is mediated by CaMKII. - Abstract: Shank is a specialized scaffold protein present in high abundance at the postsynaptic density (PSD). Using pre-embedding immunogold electron microscopy on cultured hippocampal neurons, we had previously demonstrated further accumulation of Shank at the PSD under excitatory conditions. Here, using the same experimental protocol, we demonstrate that a cell permeable CaMKII inhibitor, tatCN21, blocks NMDA-induced accumulation of Shank at the PSD. Furthermore we show that NMDA application changes the distribution pattern of Shank at the PSD, promoting a 7–10 nm shift in the median distance of Shank labels away from the postsynaptic membrane. Inhibition of CaMKII with tatCN21 also blocks this shift in the distribution of Shank. Altogether these results imply that upon activation of NMDA receptors, CaMKII mediates accumulation of Shank, preferentially at the distal regions of the PSD complex extending toward the cytoplasm.
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [2]
  1. EM Facility, NINDS, NIH, Bethesda, MD (United States)
  2. Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD (United States)
  3. Department of Pharmacology, University of Colorado Denver, School of Medicine, Aurora, CO (United States)
Publication Date:
OSTI Identifier:
22416658
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 450; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BUILDUP; CELL MEMBRANES; COMPLEXES; CYTOPLASM; DENSITY; DISTANCE; ELECTRON MICROSCOPY; INHIBITION; NERVE CELLS; RECEPTORS