Changes in phosphorylation of tau during ischemia and reperfusion in the rabbit spinal cord.
The microtubule-associated protein tau plays an important role in the dynamics of microtubule assembly necessary for axonal growth and neurite plasticity. Ischemia disrupts the neuronal cytoskeleton both by promoting proteolysis of its components and by affecting kinase and phosphatase activities that alter its assembly. In this study the effect of ischemia and reperfusion on the expression and phosphorylation of tau was examined in a reversible model of spinal cord ischemia in rabbits. tau was found to be dephosphorylated in response to ischemia with a time course that closely matched the production of permanent paraplegia. Dephosphorylation of tau was limited to the caudal lumbar spinal cord. In a similar manner, Ca2+/calmodulin-dependent kinase II activity was reduced only in the ischemic region. Thus, dephosphorylation of tau is an early marker of ischemia as is the rapid loss of Ca2+/calmodulin-dependent kinase II activity. tau, however, was rephosphorylated rapidly during reperfusion at site(s) that cause a reduction in its electrophoretic mobility regardless of the neurological outcome. Alterations in phosphorylation or degradation of tau may affect microtubule stability, possibly contributing to disruption of axonal transport but also facilitating neurite plasticity in a regenerative response.
Department of Neurosciences, University of California, San Diego, La Jolla 92093-0624, USA.
D A
DA
Shackelford
K E
KE
Nelson
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D007511:Ischemia / Q000150:complications / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D010264:Paraplegia / Q000209:etiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism*; D013116:Spinal Cord / Q000098:blood supply*; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases