Information about Tau Protein

Microtubule-associated protein tau
Identifiers
Symbol(s)	MAPT; DDPAC; FLJ31424; FTDP-17; MAPTL; MGC138549; MSTD; MTBT1; MTBT2; PPND; TAU
Function Gene Ontology • structural constituent of cytoskeleton • microtubule binding • lipoprotein binding • SH3 domain binding • enzyme binding
Orthologs
		Human	Mouse
Entrez	4137	na
Ensembl	ENSG00000186868	na
Uniprot	P10636	na
Refseq	NM_005910 (mRNA) NP_005901 (protein)	na (mRNA) na (protein)
Location	Chr 17: 0 - 0 Mb	na

Tau proteins are microtubule-associated proteins that are abundant in neurons in the central nervous system and are less common elsewhere. They were discovered in 1975 in Marc Kirschner's laboratory at Princeton University http://www.pnas.org/cgi/content/abstract/72/5/1858 Weingarten et al., 1975.

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. For example, PKN, a serine/threonine kinase. When PKN is activated, it phosphorylates tau, resulting in disruption of microtubule organization http://www.jbc.org/cgi/content/full/276/13/10025 Taniguchi et al., 2001.

Hyperphosphorylation of the tau protein (tau inclusions), however, 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 http://www.pnas.org/cgi/content/full/98/12/6923 Alonso et al., 2001.

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. Exon 2, 3 and 10 are alternative 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 no, 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). 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.

See also

• Alzheimer's Disease
• Proteopathy

Further reading

External links

• MeSH tau+Proteins

•  • [ e] Proteins of the cytoskeleton
Microfilaments	Actins - Actin-binding proteins - Actinin - Arp2/3 complex - Cofilin - Destrin - Gelsolin - Myosins - Profilin - Tropomodulin - Troponin (T, C, I) - Tropomyosin - Wiskott-Aldrich syndrome protein
Intermediate filaments	type 1 and 2 (Cytokeratin, type I, type II) - type 3 (Desmin, GFAP, Peripherin, Vimentin) - type 4 (Internexin, Nestin, Neurofilament, Synemin, Syncoilin) - type 5 (Lamin A, B)
Microtubules	Dyneins - Kinesins - MAPs (Tau protein, Dynamin) - Tubulins - Stathmin
Catenins	Alpha catenin - Beta catenin - Plakoglobin (gamma catenin) - Delta catenin
Nonhuman	Major sperm proteins - Prokaryotic cytoskeleton (Crescentin, FtsZ, MreB)
Other	APC - Dystrophin (Dystroglycan) - plakin (Desmoplakin, Plectin) - Spectrin - Talin - Utrophin - Vinculin