神經營養因子-3

神經營養因子-3
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	1B8K、1BND、1NT3、3BUK
識別號
別名	NTF3；, HDNF, NGF-2, NGF2, NT-3, NT3, neurotrophin 3
外部ID	OMIM：162660 MGI：97380 HomoloGene：1896 GeneCards：NTF3
基因位置（人類）
染色體	12號染色體
終止	5,521,536 bp
基因位置（小鼠）
染色體	小鼠6號染色體
終止	126,143,873 bp
RNA表達模式
	查閱更多表達數據
基因本體
分子功能	• neurotrophin p75 receptor binding; • neurotrophin receptor binding; • chemoattractant activity; • 生長因子活性; • signaling receptor binding; • 血漿蛋白結合;
細胞組分	• cytoplasmic vesicle; • 細胞外區域; • 細胞外空間; • 突觸小泡; • 軸突; • 樹突;
生物學過程	• regulation of apoptotic process; • negative regulation of neuron apoptotic process; • regulation of neuron differentiation; • activation of protein kinase B activity; • neuron projection morphogenesis; • activation of GTPase activity; • positive regulation of receptor internalization; • transmembrane receptor protein tyrosine kinase signaling pathway; • positive regulation of cell migration; • cell-cell signaling; • positive regulation of peptidyl-serine phosphorylation; • induction of positive chemotaxis; • negative regulation of peptidyl-tyrosine phosphorylation; • positive regulation of cell population proliferation; • positive regulation of peptidyl-tyrosine phosphorylation; • positive regulation of actin cytoskeleton reorganization; • 信號轉導; • positive chemotaxis; • 神經系統的發育; • regulation of signaling receptor activity; • positive regulation of phospholipase C activity; • positive regulation of phosphatidylinositol 3-kinase signaling; • peripheral nervous system development; • 記憶; • nerve development; • nerve growth factor signaling pathway; • modulation of chemical synaptic transmission; • positive regulation of neurotrophin TRK receptor signaling pathway;
	Sources:Amigo / QuickGO
直系同源
	4908
	18205
	ENSG00000185652
	ENSMUSG00000049107
	P20783
	P20181
	NM_001102654; NM_002527
	NM_001164034; NM_001164035; NM_008742
	NP_001096124; NP_002518
	NP_001157506; NP_001157507; NP_032768
	維基數據
檢視/編輯人類	檢視/編輯小鼠

神經營養因子-3（英文: Neurotrophin-3，NT-3）是一種由人類NTF3基因^[5]^[6]編碼的蛋白質。該蛋白屬於神經生長因子（NGF）家族，對於中樞神經系統和周圍神經系統的特定神經元有調控活性；除此以外它可以支持已存活的神經細胞的生存和分化，並促進新產生的神經元的生長和分化。NT-3是第三種被人們所知的神經營養因子，前兩種為神經生長因子（NGF）和腦源性神經營養因子（BDNF）。^[7]

功能

儘管絕大多數的哺乳動物神經元都是在胎兒期形成的，但大腦的一部分仍然保留了從神經幹細胞分化出新神經元的能力，這個過程被稱之為神經發生。神經營養因子是幫助刺激並調控這一過程的化學分子。

每個NT-3蛋白所能刺激的神經細胞數是不同的，考慮到它可以活化兩種受體酪氨酸激酶作用的神經營養分子受體（TrkC和TrkB），詳情見下面。

先天NT-3缺陷型的小鼠會喪失本體感受和部分對機械性刺激感受作用的感覺神經元。^[8]^[9]

作用機制

NT-3可以作用在下面三種細胞膜上的受體

TrkC被稱為「藥理性」受體，因為它與NT-3最為親和^[10]^[11]
NT-3也可以結合併通過與TrkC相關的受體TrkB
NT-3也可以結合Trk受體旁邊的II型細胞因子受體低親和神經生長因子受體（LNGFR）

高親和受體

TrkC是一種受體酪氨酸激酶，即它介導由於細胞上酪氨酸上添加小分子所產生的細胞信號傳導反應。

正如之前提到的，有其他的Trk相關的受體如TrkA和TrkB。也有其他類似NT-3的神經營養分子如神經生長因子（NGF）、腦源性神經營養因子（BDNF）和神經營養分子4（NT-4）。

其中TrkB受體會可以接收BDNF、NT-4和NT-3的信號，TrkA受體則被NGF所結合併活化，而TrkC則只被NT-3活化。

低親和受體

其他的NT-3受體，如LNGFR的作用相較而言較為模糊，一些研究者發現LNGFR與神經營養受體結合後可起到「水槽「的作用。

NT-3的晶體結構顯示出NT-3會形成一個同源性二聚體，兩個糖基化的p75 LNGFR分子對稱地與二聚體結合。這個對稱性的結合沿着NT-3的表面，最終在中心形成2：2的配體-受體簇。^[12]

同時表達LNGFR和Trk受體的細胞因此可能擁有更高的親和力，因為在局部會有更高的神經營養分子濃度。

另外，研究表明，LNGFR可能也參與了細胞自噬，所以那些僅表達了LNGFR蛋白而不表達Trk受體的細胞在存在神經營養因子的條件下死亡。

參考文獻

^ ^1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000185652 - Ensembl, May 2017
^ ^2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000049107 - 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.
^ Maisonpierre, Peter C.; Le Beau, Michelle M.; Espinosa, Rafael; Ip, Nancy Y.; Belluscio, Leonardo; de la Monte, Suzanne M.; Squinto, Stephen; Furth, Mark E.; Yancopoulos, George D. Human and rat brain-derived neurotrophic factor and neurotrophin-3: Gene structures, distributions, and chromosomal localizations. Genomics. 1991-07, 10 (3) [2022-11-19]. doi:10.1016/0888-7543(91)90436-I. （原始內容存檔於2022-06-20）（英語）.
^ NTF3 Gene. Definitions (Qeios). 2020-02-07.
^ Maisonpierre, PC; Belluscio, L; Squinto, S; Ip, NY; Furth, ME; Lindsay, RM; Yancopoulos, GD. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990-03-23, 247 (4949). ISSN 0036-8075. doi:10.1126/science.247.4949.1446.
^ Tessarollo, L; Vogel, K S; Palko, M E; Reid, S W; Parada, L F. Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons.. Proceedings of the National Academy of Sciences. 1994-12-06, 91 (25). ISSN 0027-8424. doi:10.1073/pnas.91.25.11844.
^ Klein, R.; Silos-Santiago, I.; Smeyne, R. J.; Lira, S. A.; Brambilla, R.; Bryant, S.; Zhang, L.; Snider, W. D.; Barbacid, M. Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements. Nature. 1994-03-17, 368 (6468) [2022-11-19]. ISSN 0028-0836. PMID 8145824. doi:10.1038/368249a0. （原始內容存檔於2022-10-17）.
^ Lamballe, Fabienne; Klein, Rüdiger; Barbacid, Mariano. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991-09, 66 (5) [2022-11-19]. doi:10.1016/0092-8674(91)90442-2. （原始內容存檔於2022-06-16）（英語）.
^ Tessarollo, L.; Tsoulfas, P.; Martin-Zanca, D.; Gilbert, D. J.; Jenkins, N. A.; Copeland, N. G.; Parada, L. F. trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues. Development (Cambridge, England). 1993-06, 118 (2) [2022-11-19]. ISSN 0950-1991. PMID 8223273. doi:10.1242/dev.118.2.463. （原始內容存檔於2022-08-21）.
^ Gong, Yong; Cao, Peng; Yu, Hong-jun; Jiang, Tao. Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex. Nature. 2008-08-07, 454 (7205) [2022-11-19]. ISSN 1476-4687. PMID 18596692. doi:10.1038/nature07089. （原始內容存檔於2022-08-08）.

外部連結

[refGRCh38Ensembl-1] 1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000185652 - Ensembl, May 2017

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000049107 - Ensembl, May 2017

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

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

[5] Maisonpierre, Peter C.; Le Beau, Michelle M.; Espinosa, Rafael; Ip, Nancy Y.; Belluscio, Leonardo; de la Monte, Suzanne M.; Squinto, Stephen; Furth, Mark E.; Yancopoulos, George D. Human and rat brain-derived neurotrophic factor and neurotrophin-3: Gene structures, distributions, and chromosomal localizations. Genomics. 1991-07, 10 (3) [2022-11-19]. doi:10.1016/0888-7543(91)90436-I. （原始內容存檔於2022-06-20）（英語）.

[6] NTF3 Gene. Definitions (Qeios). 2020-02-07.

[7] Maisonpierre, PC; Belluscio, L; Squinto, S; Ip, NY; Furth, ME; Lindsay, RM; Yancopoulos, GD. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990-03-23, 247 (4949). ISSN 0036-8075. doi:10.1126/science.247.4949.1446.

[8] Tessarollo, L; Vogel, K S; Palko, M E; Reid, S W; Parada, L F. Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons.. Proceedings of the National Academy of Sciences. 1994-12-06, 91 (25). ISSN 0027-8424. doi:10.1073/pnas.91.25.11844.

[9] Klein, R.; Silos-Santiago, I.; Smeyne, R. J.; Lira, S. A.; Brambilla, R.; Bryant, S.; Zhang, L.; Snider, W. D.; Barbacid, M. Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements. Nature. 1994-03-17, 368 (6468) [2022-11-19]. ISSN 0028-0836. PMID 8145824. doi:10.1038/368249a0. （原始內容存檔於2022-10-17）.

[10] Lamballe, Fabienne; Klein, Rüdiger; Barbacid, Mariano. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991-09, 66 (5) [2022-11-19]. doi:10.1016/0092-8674(91)90442-2. （原始內容存檔於2022-06-16）（英語）.

[11] Tessarollo, L.; Tsoulfas, P.; Martin-Zanca, D.; Gilbert, D. J.; Jenkins, N. A.; Copeland, N. G.; Parada, L. F. trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues. Development (Cambridge, England). 1993-06, 118 (2) [2022-11-19]. ISSN 0950-1991. PMID 8223273. doi:10.1242/dev.118.2.463. （原始內容存檔於2022-08-21）.

[12] Gong, Yong; Cao, Peng; Yu, Hong-jun; Jiang, Tao. Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex. Nature. 2008-08-07, 454 (7205) [2022-11-19]. ISSN 1476-4687. PMID 18596692. doi:10.1038/nature07089. （原始內容存檔於2022-08-08）.

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