title: Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration.
abstract: This review attempts to summarize what is known about tau phosphorylation in the context of both normal cellular function and dysfunction. However, conceptions of tau function continue to evolve, and it is likely that the regulation of tau distribution and metabolism is complex. The roles of microtubule-associated kinases and phosphatases have yet to be fully described, but may afford insight into how tau phosphorylation at the distal end of the axon regulates cytoskeletal-membrane interactions. Finally, lipid and glycosaminoglycan modification of tau structure affords yet more complexity for regulation and aggregation. Continued work will help to determine what is causal and what is coincidental in Alzheimer's disease, and may lead to identification of therapeutic targets for halting the progression of paired helical filament formation.
authors.affiliation: Department of Pharmacology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Billingsley
authors.forename: R L
authors.initials: RL
authors.lastname: Kincaid
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D009410:Nerve Degeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D015290:Second Messenger Systems; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D016875:tau Proteins; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases