Tau蛋白

Tau蛋白
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	1I8H、4GLR、2ON9、3OVL、4E0M、4E0N、4E0O、4FL5、4NP8、2MZ7、4TQE、4Y5I、4Y32、5DMG、4Y3B、5HF3、5E2W、5E2V
識別號
別名	MAPT；, DDPAC, FTDP-17, MAPTL, MSTD, MTBT1, MTBT2, PPND, PPP1R103, TAU, microtubule associated protein tau, Tau proteins, tau-40
外部ID	OMIM：157140 MGI：97180 HomoloGene：74962 GeneCards：MAPT
相關疾病
	間質性肺病、進行性上眼神經核麻痺症、帕金森氏症、皮克氏病、語義性失智症
基因位置（人類）
染色體	17號染色體
終止	46,028,334 bp
基因位置（小鼠）
染色體	小鼠11號染色體
終止	104,332,090 bp
RNA表現模式
	; ; ; ;
	查閱更多表現資料
基因本體
分子功能	• apolipoprotein binding; • SH3 domain binding; • tubulin binding; • 血漿蛋白結合; • lipoprotein particle binding; • 酶結合; • DNA結合; • actin binding; • microtubule binding; • dynactin binding; • receptor ligand activity; • protein phosphatase 2A binding; • Hsp90 protein binding; • minor groove of adenine-thymine-rich DNA binding; • double-stranded DNA binding; • single-stranded DNA binding; • RNA binding; • protein kinase binding; • protein-macromolecule adaptor activity; • phosphatidylinositol binding; • 相同蛋白質結合; • protein homodimerization activity; • sequence-specific DNA binding; • chaperone binding; • histone-dependent DNA binding; • microtubule lateral binding; • phosphatidylinositol bisphosphate binding;
細胞組分	• 細胞質; • cell body; • cell projection; • nuclear periphery; • 生長錐; • 神經纖維糾纏; • 細胞膜; • tubulin complex; • 樹突; • cytoplasmic ribonucleoprotein granule; • 細胞骨架; • 細胞核; • 細胞質基質; • 微管; • microtubule associated complex; • 膜; • nuclear speck; • 軸突; • somatodendritic compartment; • soma; • axon cytoplasm; • 細胞外區域; • 胞內; • 粒線體; • microtubule cytoskeleton; • axolemma; • neuron projection; • 樹突棘; • main axon; • 脂筏模型; • glial cell projection;
生物學過程	• generation of neurons; • regulation of autophagy; • regulation of microtubule polymerization; • positive regulation of microtubule polymerization; • positive regulation of axon extension; • microtubule cytoskeleton organization; • microglial cell activation; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • 訊息傳遞; • 記憶; • negative regulation of mitochondrial membrane potential; • axonal transport of mitochondrion; • cytoplasmic microtubule organization; • neuron projection development; • positive regulation of superoxide anion generation; • negative regulation of kinase activity; • cellular response to heat; • astrocyte activation; • intracellular distribution of mitochondria; • synapse organization; • regulation of calcium-mediated signaling; • protein complex oligomerization; • plus-end-directed organelle transport along microtubule; • regulation of mitochondrial fission; • negative regulation of mitochondrial fission; • 軸突運輸; • regulation of cellular response to heat; • positive regulation of neuron death; • positive regulation of protein localization to synapse; • neurofibrillary tangle assembly; • negative regulation of establishment of protein localization to mitochondrion; • positive regulation of diacylglycerol kinase activity; • regulation of response to DNA damage stimulus; • internal protein amino acid acetylation; • cell-cell signaling; • response to lead ion; • regulation of signaling receptor activity; • negative regulation of gene expression; • rRNA metabolic process; • central nervous system neuron development; • regulation of microtubule polymerization or depolymerization; • regulation of chromosome organization; • stress granule assembly; • cellular response to reactive oxygen species; • microtubule polymerization; • regulation of synaptic plasticity; • axon development; • regulation of microtubule cytoskeleton organization; • supramolecular fiber organization; • regulation of long-term synaptic depression; • positive regulation of protein localization; • negative regulation of tubulin deacetylation; • amyloid fibril formation; • cellular response to nerve growth factor stimulus; • cellular response to brain-derived neurotrophic factor stimulus;
	Sources:Amigo / QuickGO
直系同源
	4137
	17762
	ENSG00000186868; ENSG00000276155; ENSG00000277956
	ENSMUSG00000018411
	P10636
	P10637
NM_001123066; NM_001123067; NM_001203251; NM_001203252; NM_005910;
	NM_016834; NM_016835; NM_016841; NM_001377265; NM_001377266; NM_001377267; NM_001377268
	NM_001038609; NM_010838; NM_001285454; NM_001285455; NM_001285456
NP_001116538; NP_001116539; NP_001190180; NP_001190181; NP_005901;
	NP_058518; NP_058519; NP_058525; NP_001364194; NP_001364195; NP_001364196; NP_001364197
NP_001033698; NP_001272383; NP_001272384; NP_001272385; NP_034968;
	NP_001390904; NP_001390905; NP_001390906; NP_001390907; NP_001390908; NP_001390909; NP_001390910; NP_001390911; NP_001390912; NP_001390913; NP_001390916; NP_001390919; NP_001390921; NP_001390923; NP_001390925; NP_001390927; NP_001390928; NP_001390931; NP_001390933; NP_001390934; NP_001390935; NP_001390939; NP_001390940; NP_001390941; NP_001390943; NP_001390944; NP_001390945
	維基資料
檢視/編輯人類	檢視/編輯小鼠

tau蛋白（tau proteins）或作τ蛋白、濤蛋白^[6]，是一種廣泛存在於神經元軸突與胞體中的微管相關細胞骨架蛋白。在正常生理情況下，tau蛋白多與微管蛋白相結合，有促進微管聚合和穩定的作用。術語「tau」是 tubulin associated unit（微管蛋白相關單位）的縮寫。

tau蛋白屬於一種低分子量微管相關蛋白，在中樞神經系統的神經元非常豐富而少見於其它細胞，但在中樞神經系統的星形膠質細胞和少突膠質細胞中表現量也很低^[7]。在病理狀態下，tau蛋白呈過磷酸化，從微管上解離並變為不溶性，形成雙螺旋狀或直的神經原纖維（neurofibril），導致神經原纖維纏結（neurofibrillary tangles）形成，與神經系統病變（阿茲海默病）相關。

tau蛋白的多種蛋白異型體是由單個基因（人類基因組中為 MAPT，microtubule-associated protein tau，微管相關蛋白tau）mRNA的選擇性剪接而形成的^[8]^[9]。1975年，它們由Marc Kirschner在普林斯頓大學的實驗室中發現^[10]。

功能

tau蛋白是一種高度可溶的微管相關蛋白（MAP）。與非神經元細胞相較，人體內tau更多地在神經元內發現。tau蛋白的主要功能之一是維持軸突微管的穩定性。而其它神經系統中的MAPs家族蛋白也有著相似的功能，這體現在tau敲除的小鼠並沒有發現其腦組織的發育受到影響。這可能是在tau缺失後，其它MAPs家族蛋白在神經元內起到代償tau的作用，從而繼續維持軸突微管的穩定，保證腦功能的正常運作。^[11]tau並不在樹突發揮功能，而主要作用在軸突遠端維持微管的穩定性和必要的靈活性。這與MAP6蛋白（位於軸突近端固定微管）與MAP2（主要維持樹突的穩定性）的功能相對。

Tau蛋白與微管蛋白（Tubulin）相互作用以穩定微管，同時驅動Tubulin在微管內組裝。Tau蛋白通過異構和磷酸化控制微管的穩定性。

結構

六tau蛋白異構物存在於人類腦部組織中，以在結合區域中的編號為標識。其中三個異構物擁有三個結合區域，其餘三個異構物則有四個。此結合區域位於該蛋白的羥基末端並帶有正電（可與帶負電的微管結合）。而帶有四個結合區域的異構物有更好的穩定微管的功能。此異構物則為tau基因的2、3和10號外顯子被選擇性剪切的產物。

tau蛋白可視為一個在最長的tau蛋白異構物上擁有79個絲胺酸和蘇胺酸磷酸化位點的磷酸蛋白。有報道稱磷酸蛋白在普通tau蛋白的這些位點上的數量已達到30個左右。

磷酸蛋白同時也受激酶宿主的控制，包括PKN（絲胺酸/蘇胺酸蛋白激酶）。當PKN被活化，便會磷酸化tau蛋白從而造成微管組織破壞。

tau蛋白的磷酸蛋白也被先天性地控制。例如嬰兒中樞神經系統的tau蛋白的磷酸化程度比成人的更高。而所有異構物中的磷酸化程度由於磷酸酶的作用會隨著人年齡的增長而減弱。比如激酶，磷酸酶也在對這個tau蛋白的磷酸蛋白的調節中起到作用。

基因

臨床意義

tau蛋白（tau包含物，pTau）的過磷酸化（英語：Hyperphosphorylation）可導致配對的螺旋絲和直絲的纏結的自組裝，其參與阿茲海默病，額顳葉失智症，和其他tau蛋白病的發病機理^[12]。

腦損傷

相互作用

另見

Tau蛋白病變，一類與tau蛋白積累有關的疾病
慢性創傷性腦病變 (Chronic traumatic encephalopathy, CTE)
拳擊員失智症
阿茲海默病
皮質基地變性
Template:進行性核上性麻痹
蛋白質構象病
皮克氏病
17號染色體額顳葉失智症和帕金森氏症
朊病毒

參考文獻

^ 與Tau蛋白相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000186868、ENSG00000276155、ENSG00000277956 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000018411 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 楊雨哲, 孫承洲. 阿茲海默症的成因及治療 30 (3). 2014-09-30 [2015-01-23]. ISSN 2220-6493. （原始內容存檔於2015-01-23）.
^ Shin RW, Iwaki T, Kitamoto T, Tateishi J. Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues. Lab. Invest. May 1991, 64 (5): 693–702. PMID 1903170.
^ Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc. Natl. Acad. Sci. U.S.A. June 1988, 85 (11): 4051–5. PMC 280359 . PMID 3131773. doi:10.1073/pnas.85.11.4051.
^ Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. October 1989, 3 (4): 519–26. PMID 2484340. doi:10.1016/0896-6273(89)90210-9.
^ Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proc. Natl. Acad. Sci. U.S.A. May 1975, 72 (5): 1858–62. PMC 432646 . PMID 1057175. doi:10.1073/pnas.72.5.1858.
^ Harada A, Oguchi K, Okabe S, Kuno J, Terada S, Ohshima T, Sato-Yoshitake R, Takei Y, Noda T, Hirokawa N. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature. June 1994, 369 (6480): 488–91. PMID 8202139. doi:10.1038/369488a0.
^ Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K. Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. U.S.A. June 2001, 98 (12): 6923–8. PMC 34454 . PMID 11381127. doi:10.1073/pnas.121119298.

擴展閱讀

Goedert M, Crowther RA, Garner CC. Molecular characterization of microtubule-associated proteins tau and MAP2. Trends Neurosci. 1991, 14 (5): 193–9. PMID 1713721. doi:10.1016/0166-2236(91)90105-4.
Morishima-Kawashima M, Hasegawa M, Takio K; et al. Hyperphosphorylation of tau in PHF. Neurobiol. Aging. 1995, 16 (3): 365–71; discussion 371–80. PMID 7566346. doi:10.1016/0197-4580(95)00027-C.
Heutink P. Untangling tau-related dementia. Hum. Mol. Genet. 2000, 9 (6): 979–86. PMID 10767321. doi:10.1093/hmg/9.6.979.
Goedert M, Spillantini MG. Tau mutations in frontotemporal dementia FTDP-17 and their relevance for Alzheimer's disease. Biochim. Biophys. Acta. 2000, 1502 (1): 110–21. PMID 10899436. doi:10.1016/S0925-4439(00)00037-5.
Morishima-Kawashima M, Ihara Y. [Recent advances in Alzheimer's disease]. Seikagaku. 2002, 73 (11): 1297–307. PMID 11831025.
Blennow K, Vanmechelen E, Hampel H. CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease. Mol. Neurobiol. 2002, 24 (1–3): 87–97. PMID 11831556. doi:10.1385/MN:24:1-3:087.
Ingram EM, Spillantini MG. Tau gene mutations: dissecting the pathogenesis of FTDP-17. Trends in molecular medicine. 2003, 8 (12): 555–62. PMID 12470988. doi:10.1016/S1471-4914(02)02440-1.
Pickering-Brown S. The tau gene locus and frontotemporal dementia. Dementia and geriatric cognitive disorders. 2004, 17 (4): 258–60. PMID 15178931. doi:10.1159/000077149.
van Swieten JC, Rosso SM, van Herpen E; et al. Phenotypic variation in frontotemporal dementia and parkinsonism linked to chromosome 17. Dementia and geriatric cognitive disorders. 2004, 17 (4): 261–4. PMID 15178932. doi:10.1159/000077150.
Kowalska A, Jamrozik Z, Kwieciński H. Progressive supranuclear palsy--parkinsonian disorder with tau pathology. Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences. 2004, 42 (2): 119–23. PMID 15266787.
Rademakers R, Cruts M, van Broeckhoven C. The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum. Mutat. 2005, 24 (4): 277–95. PMID 15365985. doi:10.1002/humu.20086.
Lee HG, Perry G, Moreira PI; et al. Tau phosphorylation in Alzheimer's disease: pathogen or protector?. Trends in molecular medicine. 2005, 11 (4): 164–9. PMID 15823754. doi:10.1016/j.molmed.2005.02.008.
Hardy J, Pittman A, Myers A; et al. Evidence suggesting that Homo neanderthalensis contributed the H2 MAPT haplotype to Homo sapiens. Biochem. Soc. Trans. 2005, 33 (Pt 4): 582–5. PMID 16042549. doi:10.1042/BST0330582.
Deutsch SI, Rosse RB, Lakshman RM. Dysregulation of tau phosphorylation is a hypothesized point of convergence in the pathogenesis of alzheimer's disease, frontotemporal dementia and schizophrenia with therapeutic implications. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2007, 30 (8): 1369–80. PMID 16793187. doi:10.1016/j.pnpbp.2006.04.007.
Williams DR. Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau. Internal medicine journal. 2006, 36 (10): 652–60. PMID 16958643. doi:10.1111/j.1445-5994.2006.01153.x.
Pittman AM, Fung HC, de Silva R. Untangling the tau gene association with neurodegenerative disorders. Hum. Mol. Genet. 15. 2006,. Spec No 2 (Review Issue 2): R188–95. PMID 16987883. doi:10.1093/hmg/ddl190.
Roder HM, Hutton ML. Microtubule-associated protein tau as a therapeutic target in neurodegenerative disease. Expert Opin. Ther. Targets. 2007, 11 (4): 435–42. PMID 17373874. doi:10.1517/14728222.11.4.435.
van Swieten J, Spillantini MG. Hereditary frontotemporal dementia caused by Tau gene mutations. Brain Pathol. 2007, 17 (1): 63–73. PMID 17493040. doi:10.1111/j.1750-3639.2007.00052.x.
Caffrey TM, Wade-Martins R. Functional MAPT haplotypes: bridging the gap between genotype and neuropathology. Neurobiol. Dis. 2007, 27 (1): 1–10. PMC 2801069 . PMID 17555970. doi:10.1016/j.nbd.2007.04.006.
Delacourte A. Tauopathies: recent insights into old diseases. Folia Neuropathol. 2005, 43 (4): 244–57. PMID 16416389.
Hirokawa N, Shiomura Y, Okabe S. Tau proteins: the molecular structure and mode of binding on microtubules. J. Cell Biol. October 1988, 107 (4): 1449–59. PMC 2115262 . PMID 3139677. doi:10.1083/jcb.107.4.1449.

外部連結

醫學主題詞表（MeSH）：tau+Proteins
GeneReviews/NCBI/NIH/UW entry on MAPT-Related Disorders（頁面存檔備份，存於網際網路檔案館）
MR scans of variant CJD CSF Tau positive man

[1] 與Tau蛋白相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000186868、ENSG00000276155、ENSG00000277956 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000018411 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[6] 楊雨哲, 孫承洲. 阿茲海默症的成因及治療 30 (3). 2014-09-30 [2015-01-23]. ISSN 2220-6493. （原始內容存檔於2015-01-23）.

[pmid1903170-7] Shin RW, Iwaki T, Kitamoto T, Tateishi J. Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues. Lab. Invest. May 1991, 64 (5): 693–702. PMID 1903170.

[pmid3131773-8] Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc. Natl. Acad. Sci. U.S.A. June 1988, 85 (11): 4051–5. PMC 280359 . PMID 3131773. doi:10.1073/pnas.85.11.4051.

[pmid2484340-9] Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. October 1989, 3 (4): 519–26. PMID 2484340. doi:10.1016/0896-6273(89)90210-9.

[pmid1057175-10] Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proc. Natl. Acad. Sci. U.S.A. May 1975, 72 (5): 1858–62. PMC 432646 . PMID 1057175. doi:10.1073/pnas.72.5.1858.

[pmid8202139-11] Harada A, Oguchi K, Okabe S, Kuno J, Terada S, Ohshima T, Sato-Yoshitake R, Takei Y, Noda T, Hirokawa N. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature. June 1994, 369 (6480): 488–91. PMID 8202139. doi:10.1038/369488a0.

[pmid11381127-12] Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K. Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. U.S.A. June 2001, 98 (12): 6923–8. PMC 34454 . PMID 11381127. doi:10.1073/pnas.121119298.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]