Tau蛋白

Microtubule-associated protein tau
微管相關蛋白tau
Microtubule-associated protein tau; 微管相關蛋白tau
	蛋白質資料庫計算機所繪製的連接在P1NI蛋白的結合區域上的MAPT片段
有效結構
PDB	直系同源檢索：PDBe, RCSB
PDB查詢代碼列表
	1I8H, 3FQP, 3OVL, 4E0M, 4E0N, 4E0O, 4GLR
標識
代號	MAPT; DDPAC; FTDP-17; MAPTL; MSTD; MTBT1; MTBT2; PPND; TAU
擴展標識	遺傳學：157140 同源基因：74962 ChEMBL: 1293224 GeneCards: MAPT Gene
基因本體論描述
分子功能	· structural constituent of cytoskeleton; · protein binding; · microtubule binding; · SH3 domain binding; · enzyme binding; · protein kinase binding; · apolipoprotein binding; · lipoprotein particle binding;
細胞成分	· cytosol; · microtubule; · microtubule associated complex; · plasma membrane; · axon; · growth cone; · nuclear periphery; · cilium axoneme; · tubulin complex;
生物過程	· microtubule cytoskeleton organization; · neuron migration; · apoptotic process; · cellular component disassembly involved in execution phase of apoptosis; · axonogenesis; · adult walking behavior; · axon cargo transport; · regulation of autophagy; · regulation of microtubule polymerization; · positive regulation of microtubule polymerization; · negative regulation of intracellular transport; · positive regulation of axon extension; · mitochondrion transport along microtubule; · generation of neurons; · regulation of microtubule-based movement;
	Sources: Amigo / QuickGO
RNA表達模式
	更多表達數據
直系同源體
物種	人類
Entrez	4137
Ensembl	ENSG00000186868
UniProt	P10636
mRNA序列	NM_001123066
蛋白序列	NP_001116538
基因位置	Chr 17:; 43.97 – 44.11 Mb
PubMed查詢	[1]
	閱; 論; 編;

Tau蛋白（英語：Tau proteins；「Tau」為「Tubulin associated unit」即「微管蛋白相關單位」的縮寫），又譯濤蛋白^[1]。是一種微管相關蛋白，在中樞神經系統的神經元非常豐富而少見於其它細胞，在中樞神經系統的星形膠質細胞和少突膠質細胞中表達量也很低^[2]。tau蛋白有缺陷並不再正常穩定微管時，可導致神經系統病變和失智症，如阿茲海默病。

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^[3]^[4]。1975年，它們由Marc Kirschner在普林斯頓大學的實驗室中發現^[5]。

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家族蛋白也有着相似的功能，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。^[6] 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蛋白異構體存在於人類腦部組織中，以在結合區域中的編號為標識。其中三個異構體擁有三個結合區域，其餘三個異構體則有四個。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體有更好的穩定微管的功能。此異構體則為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蛋白異構體上擁有79個絲氨酸和蘇氨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（絲氨酸/蘇氨酸蛋白激酶）。當PKN被激活，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。而所有異構體中的磷酸化程度由於磷酸酶的作用會隨着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）的過度磷酸化（英語：Hyperphosphorylation）可導致配對的螺旋絲和直絲的纏結的自組裝，其參與阿茲海默症，額顳葉痴呆，和其他tau蛋白病的發病機理^[7]。

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)
拳擊員痴呆
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號染色體額顳葉痴呆症和帕金森氏症
朊病毒

參考文獻

^ 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.

進一步閱讀

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] 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）.

[pmid1903170-2] 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.

[pmid3131773-3] 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.

[pmid2484340-4] 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.

[pmid1057175-5] 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.

[pmid8202139-6] 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.

[pmid11381127-7] 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.

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