NMDA receptor stimulation induces reversible fission of the neuronal endoplasmic reticulum.
Research output: Contribution to journal › Article
With few exceptions the endoplasmic reticulum (ER) is considered a continuous system of endomembranes within which proteins and ions can move. We have studied dynamic structural changes of the ER in hippocampal neurons in primary culture and organotypic slices. Fluorescence recovery after photobleaching (FRAP) was used to quantify and model ER structural dynamics. Ultrastructure was assessed by electron microscopy. In live cell imaging experiments we found that, under basal conditions, the ER of neuronal soma and dendrites was continuous. The smooth and uninterrupted appearance of the ER changed dramatically after glutamate stimulation. The ER fragmented into isolated vesicles in a rapid fission reaction that occurred prior to overt signs of neuronal damage. ER fission was found to be independent of ER calcium levels. Apart from glutamate, the calcium ionophore ionomycin was able to induce ER fission. The N-methyl, D-aspartate (NMDA) receptor antagonist MK-801 inhibited ER fission induced by glutamate as well as by ionomycin. Fission was not blocked by either ifenprodil or kinase inhibitors. Interestingly, sub-lethal NMDA receptor stimulation caused rapid ER fission followed by fusion. Hence, ER fission is not strictly associated with cellular damage or death. Our results thus demonstrate that neuronal ER structure is dynamically regulated with important consequences for protein mobility and ER luminal calcium tunneling.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Publication status||Published - 2009|
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Brain Research (0131000120), Computational biology and biological physics (000006113), Laboratory for Experimental Brain Research (013041000), Faculty of Medicine (000022000), Clinical Memory Research Unit (013242610)
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Related research output
Krzysztof Kucharz, 2010, Department of Clinical Sciences, Lund University. 106 p.
Research output: Thesis › Doctoral Thesis (compilation)