AI Article Synopsis
- In neurodegenerative conditions, the mismanagement of calcium ions (Ca(2+)) and damage to the cytoskeleton harm neuron health, yet the role of cytoskeletal proteins in signaling has not been fully studied.
- The protein p600, a microtubule-associated protein, is found to promote neuronal survival by influencing calcium homeostasis, especially when induced by the activation of NMDA receptors.
- The interaction between p600 and calmodulin is crucial as it helps protect neurons from specific death pathways linked to calcium overload, highlighting the importance of p600 in maintaining neuronal integrity.
Article Abstract
In acute and chronic neurodegeneration, Ca(2+) mishandling and disruption of the cytoskeleton compromise neuronal integrity, yet abnormalities in the signaling roles of cytoskeletal proteins remain largely unexplored. We now report that the microtubule-associated protein p600 (also known as UBR4) promotes neuronal survival. Following depletion of p600, glutamate-induced Ca(2+) influx through NMDA receptors, but not AMPA receptors, initiates a degenerative process characterized by endoplasmic reticulum fragmentation and endoplasmic reticulum Ca(2+) release via inositol 1,4,5-trisphosphate receptors. Downstream of NMDA receptors, p600 associates with the calmodulin·calmodulin-dependent protein kinase IIα complex. A direct and atypical p600/calmodulin interaction is required for neuronal survival. Thus, p600 counteracts specific Ca(2+)-induced death pathways through regulation of Ca(2+) homeostasis and signaling.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750145 | PMC |
| http://dx.doi.org/10.1074/jbc.M113.483107 | DOI Listing |
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