title: NMDA-induced accumulation of Shank at the postsynaptic density 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: EM Facility, NINDS, NIH, Bethesda, MD, United States.
authors: Jung-Hwa
authors: JH
authors: Tao-Cheng
authors: Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD, United States.
authors: Yijung
authors: Y
authors: Yang
authors: Department of Pharmacology, University of Colorado Denver, School of Medicine, Aurora, CO, United States.
authors: K Ulrich
authors: KU
authors: Bayer
authors: Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD, United States.
authors: Thomas S
authors: TS
authors: Reese
authors: Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD, United States. Electronic address: dosemeca@ninds.nih.gov.
authors: Ayse
authors: A
authors: Dosemeci
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D057907:Post-Synaptic Density / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009419:Nerve Tissue Proteins; D016202:N-Methylaspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: CaMKII; Homer; PSD; ProSAP; Shank; tatCN21