MAPT
GeneName
MAPT
Summary
MAPT, commonly referred to as tau or microtubule associated protein tau, is a 79 kDa protein that is predominantly expressed in neurons and plays a critical role in stabilising microtubules, which are essential for maintaining neuronal structure and function. It is localised in various cellular compartments including the axon, dendrites, and cytoplasm, and is involved in several key biological processes such as axonal transport, neuron projection development, and microtubule polymerization. Tau is also implicated in the formation of neurofibrillary tangles, a hallmark of neurodegenerative diseases like Alzheimer’s. Additionally, it has multiple binding functions, including interactions with microtubules, actin, and various proteins involved in cellular signalling and transport.
Importance
MAPT is relevant to: - Neurodegenerative diseases, particularly Alzheimer’s disease, due to its role in tau pathology and neurofibrillary tangle formation. - Neuronal development and synaptic plasticity, as it is crucial for axon development and the regulation of microtubule dynamics. - Cellular responses to stress and signalling mechanisms, given its involvement in stress granule assembly and response to reactive oxygen species. - The study of cellular transport mechanisms, as it is integral to axonal transport processes and mitochondrial distribution within neurons.
Top Products
For researchers investigating MAPT, we recommend two excellent primary antibodies that cater to different experimental needs. The first is the well-cited polyclonal antibody, Anti-Tau antibody (ab75714), which has garnered 32 citations and is particularly effective for immunohistochemistry (IHC). This antibody is a trusted choice for those focusing on tissue samples. In addition, we offer the recombinant monoclonal antibody, Anti-Tau antibody [EP2456Y] (ab76128). This product has been validated in a range of applications, including Western blotting (WB), IHC, immunocytochemistry (ICC), and flow cytometry (FC), making it a versatile option for various experimental setups. With 33 citations, it demonstrates a strong presence in the research community. Together, these antibodies provide robust tools for studying MAPT effectively. "The Human Tau ELISA Kit (ab273617), with 4 citations, is an excellent option for researchers looking to measure MAPT levels in their samples."
Abcam Product Citation Summary
The data indicates a strong focus on the role of MAPT (tau protein) in various neurological contexts, particularly in mouse models. Studies often explore tau's involvement in conditions such as Alzheimer's disease, cognitive impairment, and synaptic signaling related to obesity. The use of both Western blotting and immunocytochemistry highlights the importance of MAPT in understanding tau phosphorylation and its implications in neurodegenerative diseases.
Abcam Product Citation Table
Developmental stage
Four-repeat (type II) TAU/MAPT is expressed in an adult-specific manner and is not found in fetal brain, whereas three-repeat (type I) TAU/MAPT is found in both adult and fetal brain.
Domain
The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats.
Function
Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization.
Involvement in disease
In Alzheimer disease, the neuronal cytoskeleton in the brain is progressively disrupted and replaced by tangles of paired helical filaments (PHF) and straight filaments, mainly composed of hyperphosphorylated forms of TAU (PHF-TAU or AD P-TAU). O-GlcNAcylation is greatly reduced in Alzheimer disease brain cerebral cortex leading to an increase in TAU/MAPT phosphorylations.
Frontotemporal dementia 1
FTD1
A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, 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.
None
The disease is caused by variants affecting the gene represented in this entry.
Pick disease of the brain
PIDB
A rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
Progressive supranuclear palsy 1
PSNP1
Characterized by akinetic-rigid syndrome, supranuclear gaze palsy, pyramidal tract dysfunction, pseudobulbar signs and cognitive capacities deterioration. Neurofibrillary tangles and gliosis but no amyloid plaques are found in diseased brains. Most cases appear to be sporadic, with a significant association with a common haplotype including the MAPT gene and the flanking regions. Familial cases show an autosomal dominant pattern of transmission with incomplete penetrance; genetic analysis of a few cases showed the occurrence of tau mutations, including a deletion of Asn-613.
None
The disease is caused by variants affecting the gene represented in this entry.
Parkinson-dementia syndrome
PARDE
A syndrome characterized by parkinsonism, tremor, rigidity, dementia, ophthalmoparesis and pyramidal signs. Neurofibrillary degeneration occurs in the hippocampus, basal ganglia and brainstem nuclei.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at serine and threonine residues in S-P or T-P motifs by proline-directed protein kinases (PDPK1, CDK1, CDK5, GSK3, MAPK) (only 2-3 sites per protein in interphase, seven-fold increase in mitosis, and in the form associated with paired helical filaments (PHF-tau)), and at serine residues in K-X-G-S motifs by MAP/microtubule affinity-regulating kinase (MARK1, MARK2, MARK3 or MARK4), causing detachment from microtubules, and their disassembly (PubMed:23666762, PubMed:7706316). Phosphorylation decreases with age. Phosphorylation within tau/MAP's repeat domain or in flanking regions seems to reduce tau/MAP's interaction with, respectively, microtubules or plasma membrane components (PubMed:7706316). Phosphorylation on Ser-610, Ser-622, Ser-641 and Ser-673 in several isoforms during mitosis. Phosphorylation at Ser-548 by GSK3B reduces ability to bind and stabilize microtubules. Phosphorylation at Ser-579 by BRSK1 and BRSK2 in neurons affects ability to bind microtubules and plays a role in neuron polarization. Phosphorylated at Ser-554, Ser-579, Ser-602, Ser-606 and Ser-669 by PHK. Phosphorylation at Ser-214 by SGK1 mediates microtubule depolymerization and neurite formation in hippocampal neurons. There is a reciprocal down-regulation of phosphorylation and O-GlcNAcylation. Phosphorylation on Ser-717 completely abolishes the O-GlcNAcylation on this site, while phosphorylation on Ser-713 and Ser-721 reduces glycosylation by a factor of 2 and 4 respectively. Phosphorylation on Ser-721 is reduced by about 41.5% by GlcNAcylation on Ser-717. Dephosphorylated at several serine and threonine residues by the serine/threonine phosphatase PPP5C.
Polyubiquitinated. Requires functional TRAF6 and may provoke SQSTM1-dependent degradation by the proteasome (By similarity). PHF-tau can be modified by three different forms of polyubiquitination. 'Lys-48'-linked polyubiquitination is the major form, 'Lys-6'-linked and 'Lys-11'-linked polyubiquitination also occur.
O-glycosylated. O-GlcNAcylation content is around 8.2%. There is reciprocal down-regulation of phosphorylation and O-GlcNAcylation. Phosphorylation on Ser-717 completely abolishes the O-GlcNAcylation on this site, while phosphorylation on Ser-713 and Ser-721 reduces O-GlcNAcylation by a factor of 2 and 4 respectively. O-GlcNAcylation on Ser-717 decreases the phosphorylation on Ser-721 by about 41.5%.
Glycation of PHF-tau, but not normal brain TAU/MAPT. 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.
Tissue Specificity
Expressed in neurons. Isoform PNS-tau is expressed in the peripheral nervous system while the others are expressed in the central nervous system.
Cellular localization
- Cytoplasm
- Cytosol
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasm
- Cytoskeleton
- Cell projection
- Axon
- Cell projection
- Dendrite
- Secreted
- Mostly found in the axons of neurons, in the cytosol and in association with plasma membrane components (PubMed:10747907). Can be secreted; the secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (PubMed:32272059).
Alternative names
MAPTL, MTBT1, TAU, MAPT, Microtubule-associated protein tau, Neurofibrillary tangle protein, Paired helical filament-tau, PHF-tau
Database links
swissprot:P10636 omim:157140 swissprot:P10636-2 swissprot:P10636-6 entrezGene:4137