Phosphorylation of tau alters its association with the plasma membrane.
1. The potential functions of the microtubule-associated protein tau have been expanded by the recent demonstration of its interaction with the plasma membrane. Since the association of tau with microtubules is regulated by phosphorylation, herein we examine whether or not the association of tau with the plasma membrane is also regulated by phosphorylation. 2. A range of tau isoforms migrating from 46 to 64 kDa was associated with crude particulate fractions derived from SH-SY-5Y human neuroblastoma cells, and were retained during the initial stages of plasma membrane purification. During the extensive washing utilized in purification of the plasma membrane, portions of each of these isoforms were depleted from the resultant purified membrane. Immunoblot analysis with phospho-dependent and -independent antibodies revealed selective depletion of phospho isoforms during membrane washing. This effect was more pronounced for the slowest-migrating (64-kDa) tau isoform. 3. This putative influence of phosphorylation on the association of tau with the plasma membrane was further probed by transfection of SH-SY-5Y human neuroblastoma cells with a tau construct that could associate with the plasma membrane but not with microtubules. Treatment with phorbol ester or calcium ionophore, both of which increased phospho-tau levels within the cytosol and plasma membrane, was accompanied by the dissociation of this tau construct from the membrane. 4. These data indicate that phosphorylation regulates the association with the plasma membrane. Dissociation from the membrane by phosphorylation may place tau at risk for hyperphosphorylation and ultimate PHF formation in a manner previously considered for tau dissociated from microtubules.
Ekinci
F J
FJ
Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts at Lowell, 01854, USA.
Shea
T B
TB
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000378:metabolism*
D020033:Protein Isoforms; D016875:tau Proteins