Short Description of Tau Protein

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Tau protein

Microtubule-associated protein tau
Identifiers
Symbols	MAPT; DDPAC; FLJ31424; FTDP-17; MAPTL; MGC138549; MSTD; MTBT1; MTBT2; PPND; TAU
External IDs	OMIM: 157140 HomoloGene: 44834 GeneCards: MAPT Gene
[show]Gene Ontology Molecular function • structural constituent of cytoskeleton • microtubule binding • lipoprotein binding • SH3 domain binding • enzyme binding Cellular component • cytosol • cytoskeleton • microtubule associated complex • plasma membrane • axon • growth cone • tubulin complex Biological process • microtubule cytoskeleton organization and biogenesis • negative regulation of microtubule depolymerization • positive regulation of microtubule polymerization • positive regulation of axon extension • generation of neurons Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4137	17762
Ensembl	ENSG00000186868	ENSMUSG00000018411
UniProt	P10636	P10637
RefSeq (mRNA)	NM_005910	NM_001038609.1
RefSeq (protein)	NP_005901	NP_001033698.1
Location (UCSC)	Chr 17: 41.33 - 41.46 Mb	Chr 11: 103.99 - 104.19 Mb
PubMed search	[1]	[2]

Tau proteins

They are the proteins that stabilize microtubules. They are abundant in neurons in the central nervous system and are less common elsewhere. When tau proteins are defective, and no longer stabilize microtubules properly, they can result in dementias, such as Alzheimer's disease.

The tau proteins are the product of alternative splicing from a single gene that in humans is designated MAPT.^[1][2] They were discovered in 1975 in Marc Kirschner's laboratory at Princeton University.^[3]

 Function

Tau proteins interact with tubulin to stabilize microtubules and promote tubulin assembly into microtubules. Tau has two ways of controlling microtubule stability: isoforms and phosphorylation. Six tau isoforms exist in brain tissue, and they are distinguished by their number of binding domains. Three isoforms have three binding domains and the other three have four binding domains. The binding domains are located in the carboxy-terminus of the protein and are positively-charged (allowing it to bind to the negatively-charged microtubule). The isoforms with four binding domains are better at stabilizing microtubules than those with three binding domains. The isoforms are a result of alternative splicing in exons 2, 3, and 10 of the tau gene.

Phosphorylation of tau is regulated by a host of kinases, including PKN, a serine/threonine kinase. When PKN is activated, it phosphorylates tau, resulting in disruption of microtubule organization.^[4]Tau protein is a highly soluble microtubule-associated protein (MAP). In humans, these proteins are mostly found in neurons compared to non-neuronal cells. One of tau's main functions is to modulate the stability of axonal microtubules. Tau is not present in dendrites and is active primarily in the distal portions of axons where it provides microtubule stabilization but also flexibility as needed. This contrasts with STOP proteins in the proximal portions of axons which essentially lock down the microtubules and MAP2 that stabilizes microtubules in dendrites. The tau gene locates on chromosome 17q21, containing 16 exons. The major tau protein in the human brain is encoded by 11 exons. Exons 2, 3 and 10 are alternatively spliced, allowing six combinations (2^–3^–10^–; 2⁺3^–10^–; 2⁺3⁺10^–; 2^–3^–10⁺; 2⁺3^–10⁺; 2⁺3⁺10⁺). Thus, in the human brain, the tau proteins constitute a family of six isoforms with the range from 352-441 amino acids. They differ in either zero, one or two inserts of 29 amino acids at the N-terminal part (exon 2 and 3), and three or four repeat-regions at the C-terminal part exon 10 missing. So, the longest isoform in the CNS has four repeats (R1, R2, R3 and R4) and two inserts (441 amino acids total), while the shortest isoform has three repeats (R1, R3 and R4) and no insert (352 amino acids total).

 Role in disease

Further information: Tauopathy

Hyperphosphorylation of the tau protein (tau inclusions, pTau) can result in the self-assembly of tangles of paired helical filaments and straight filaments, which are involved in the pathogenesis of Alzheimer's disease and other tauopathies.^[5]

All of the six tau isoforms are present in an often hyperphosphorylated state in paired helical filaments from Alzheimer's disease brain. In other neurodegenerative diseases, the deposition of aggregates enriched in certain tau isoforms has been reported. When misfolded, this otherwise very soluble protein can form extremely insoluble aggregates that contribute to a number of neurodegenerative diseases.