Tau phospho S409

GWB-10EF47

Synthetic peptide (Human) derived from a region of human tau that contains serine 409.

Phosphorylation site-specific antibody selective for the phosphorylated form of human tau containing a phosphate on serine 409.

Tau

Purified from rabbit serum by sequential epitope-specific chromatography. The antibody has been negatively preadsorbed using a non-phosphopeptide corresponding to the site of phosphorylation to remove antibody that is reactive with non-phosphorylated tau. The final product is generated by affinity chromatography using a tau-derived peptide that is phosphorylated at serine 409. Storage

WB: Use at a dilution of 1/1000. Predicted

Mostly found in the axons of neurons in the cytosol and in association with plasma membrane components. Tau is a neuronal microtubule-associated protein found predominantly on axons. The function of tau is to promote tubulin polymerisation and stabilise microtubules but it also serves to link certain signalling pathways to the cytoskeleton. Tau in its hyperphosphorylated form is the major component of paired helical filaments (PHF) the building block of neurofibrillary lesions in Alzheimerí s disease (AD) brain. Hyperphosphorylation impairs the microtubule binding function of tau resulting in the destabilisation of microtubules in AD brains ultimately leading to the degeneration of the affected neurons. Hyperphosphorylated tau is also found in a range of other central nervous system disorders. Numerous serine/threonine kinases including GSK 3 beta PKA Cdk 5 and casein kinase II can phosphorylate tau. Phosphopeptide mapping shows that serine 409 is phosphorylated by protein kinase A in vitro. This site has also been shown to be phosphorylated in situ in brains from Alzheimerí s patients.

Interacts with PSMC2 through SQSTM1 (By similarity). Interacts with SQSTM1 when polyubiquitinated.

Expressed in neurons. Isoform PNS-tau is expressed in the peripheral nervous system while the others are expressed in the central nervous system. Developmental Stage: Four-repeat (type II) tau is expressed in an adult-specific manner and is not found in fetal brain whereas three-repeat (type I) tau is found in both adult and fetal brain.

Phosphorylation at serine and threonine residues in S-P or T-P motifs by proline-directed protein kinases (PDPK: CDC2 CDK5 GSK-3 MAPK) (only 2-3 sites per protein in interphase seven-fold increase in mitosis and in PHF-tau) and at serine residues in K-X-G-S motifs by MAP/microtubule affinity-regulating kinase (MARK) in Alzheimer diseased brains. Phosphorylation decreases with age. Phosphorylation within tau\' s repeat domain or in flanking regions seems to reduce tau\' s interaction with respectively microtubules or plasma membrane components. Phosphorylation on Ser-610 Ser-622 Ser-641 and Ser-673 in several isoforms during mitosis.

Glycation of PHF-tau but not normal brain tau. Glycation is a non-enzymatic post-translational modification that involves a covalent linkage between a sugar and an amino group of a protein molecule forming ketoamine. Subsequent oxidation fragmentation and/or cross-linking of ketoamine leads to the production of advanced glycation endproducts (AGES). Glycation may play a role in stabilizing PHF aggregation leading to tangle formation in AD.

Defects in MAPT are a cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP17) [MIM:600274 172700]; also called frontotemporal dementia (FTD) or historically termed Pick complex. This form of frontotemporal dementia is characterized by presenile dementia with behavioral changes deterioration of cognitive capacities and loss of memory. In some cases parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia substantia nigra amygdala. In most cases protein tau deposits are found in glial cells and/or neurons.

Defects in MAPT are a cause of corticobasal degeneration (CBD). It is marked by extrapyramidal signs and apraxia and can be associated with memory loss. Neuropathologic features may overlap Alzheimer disease progressive supranuclear palsy and Parkinson disease.

Defects in MAPT may be a cause of hereditary dysphasic disinhibition dementia (HDDD) [MIM:607485]. HDDD is a frontotemporal dementia characterized by progressive cognitive deficits with memory loss and personality changes severe dysphasic disturbances leading to mutism and hyperphagia. Similarity: Contains 4 Tau/MAP repeats.