Neurofilament tail phosphorylation: identity of the RT-97 phosphoepitope and regulation in neurons by cross-talk among proline-directed kinases.

Journal of Neurochemistry
VeerannaR A Nixon

Abstract

As axons myelinate, establish a stable neurofilament network, and expand in caliber, neurofilament proteins are extensively phosphorylated along their C-terminal tails, which is recognized by the monoclonal antibody, RT-97. Here, we demonstrate in vivo that RT-97 immunoreactivity (IR) is generated by phosphorylation at KSPXK or KSPXXXK motifs and requires flanking lysines at specific positions. extracellular signal regulated kinase 1,2 (ERK1,2) and pERK1,2 levels increase in parallel with phosphorylation at the RT-97 epitope during early postnatal brain development. Purified ERK1,2 generated RT-97 on both KSP motifs on recombinant NF-H tail domain proteins, while cdk5 phosphorylated only KSPXK motifs. RT-97 epitope generation in primary hippocampal neurons was regulated by extensive cross-talk among ERK1,2, c-Jun N-terminal kinase 1,2 (JNK1,2) and cdk5. Inhibition of both ERK1,2 and JNK1,2 completely blocked RT-97 generation. Cdk5 influenced RT-97 generation indirectly by modulating JNK activation. In mice, cdk5 gene deletion did not significantly alter RT-97 IR or ERK1,2 and JNK activation. In mice lacking the cdk5 activator P35, the partial suppression of cdk5 activity increased RT-97 IR by activating ERK1,2. Thus, cdk5 influ...Continue Reading

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Citations

Jul 14, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Parvathi RudrabhatlaHarish C Pant
Jan 19, 2012·Journal of Biomedical Science·Wen-Ching LeeChung-Liang Chien
May 22, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nael H AlamiAnthony Brown
Feb 28, 2009·Trends in Molecular Medicine·Diane P HangerWendy Noble
Jan 3, 2013·Journal of the Peripheral Nervous System : JPNS·Anne HolmgrenVincent Timmerman

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