کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4337924 1614832 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of CaMKII inhibitor tatCN21 on activity-dependent redistribution of CaMKII in hippocampal neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Effects of CaMKII inhibitor tatCN21 on activity-dependent redistribution of CaMKII in hippocampal neurons
چکیده انگلیسی


• The CaMKII inhibitor, tatCN21, blocks NMDA-induced accumulation of CaMKII at the PSD.
• TatCN21 blocks activity-induced CaMKII clusters in dendrites.
• TatCN21 induces the formation of CaMKII–polyribosome aggregate near PSD and in dendrites.
• Formation of aggregates is enhanced by excitation and depends on the dose of tatCN21.
• Formation of CaMKII–polyribosome aggregates is calcium dependent and reversible.

TatCN21 is a membrane permeable calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor derived from the inhibitor protein CaMKIIN. TatCN21 has been used to demonstrate the involvement of CaMKII in a variety of physiological and pathological phenomena, and it also limits excitotoxic damage in neurons. Here we use preembedding immunogold electron microscopy to examine the effect of tatCN21 on the redistribution of CaMKII in cultured hippocampal neurons. Incubation of cultures with tatCN21 (20 μM for 20 min) prior to exposure to N-methyl-d-asparic acid (NMDA) (50 μM for 2 min) inhibited both the accumulation of CaMKII at postsynaptic densities (PSDs) and CaMKII clustering in the dendrites. Under these conditions, CaMKII also formed morphologically distinct aggregates with polyribosomes near the PSD and in dendrites. Formation of these CaMKII–polyribosome aggregates requires the presence of both tatCN21 and calcium, and was augmented upon exposure to high K+ or NMDA. CaMKII–polyribosome aggregates formed consistently with 20 μM tatCN21, but minimally or not at all with 5 μM. However, these aggregates are not induced by another CaMKII inhibitor, KN93. Formation of CaMKII–polyribosome aggregates was completely reversible within 1 h after washout of tatCN21. Effects of tatCN21 were largely restricted to dendrites, with minimal effect in the soma. The effects of tatCN21 on CaMKII distribution can be used to dissect the mechanism of CaMKII involvement in cellular events.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 244, 6 August 2013, Pages 188–196
نویسندگان
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