Atg9a deficiency causes axon-specific lesions including neuronal circuit dysgenesis.
Atg9a deficiency causes axon-specific lesions including neuronal circuit dysgenesis.
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ATG9A缺乏会导致轴突特异性病变，包括神经元电路失调。
DOI：
10.1080/15548627.2017.1314897
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发表时间：
2018
期刊：
影响因子：
13.3
通讯作者：
Uchiyama Y
中科院分区：
文献类型：
--
作者：
Yamaguchi J;Suzuki C;Nanao T;Kakuta S;Ozawa K;Tanida I;Saitoh T;Sunabori T;Komatsu M;Tanaka K;Aoki S;Sakimura K;Uchiyama Y
培养 Atg9a（特别是脑组织）的条件性敲除小鼠，以了解 ATG9A 在神经组织细胞中的作用。这些小鼠出生正常，但其中一半在一周内死亡，并且没有一只活过 4 周。选择性自噬的受体蛋白 SQSTM1/p62 和 NBR1 与泛素一起在出生后 15 天（P15）在 Atg9a 缺陷的神经瘤中积累，表明自噬受到抑制，而免疫组织化学、电子显微镜和蛋白质印迹证明，这些蛋白在 P28 时显着减少。相反，在 P28 处被异常膜结构和无定形材料占据的轴突及其末端发生诸如神经纤维束海绵化等退行性变化，尽管在神经元细胞体中没有检测到明显的退行性变化。与自噬不同，弥散张量磁共振成像和组织学观察揭示Atg9a缺陷导致胼胝体和前连合发育不全。至于原代培养神经元的神经突延伸，培养 3 天后，atg9a-KO 小鼠大脑的原代神经元的神经突生长明显受损，但 atg7-KO 和 atg16l1-KO 大脑的原代神经元则没有。此外，这种趋势也在 atg7-KO 背景下的 Atg9a 敲低神经元中得到证实，表明 ATG9A 在独立于自噬的神经突生长调节中的作用。这些结果表明 Atg9a 缺陷会导致轴突及其末端的进行性退化，但不会导致神经元细胞体的退化，其中 SQSTM1/p62 和 NBR1 的降解未得到充分抑制。此外，Atg9a 的缺失会损害神经纤维束的形成。
Conditional knockout mice for Atg9a, specifically in brain tissue, were generated to understand the roles of ATG9A in the neural tissue cells. The mice were born normally, but half of them died within one wk, and none lived beyond 4 wk of age. SQSTM1/p62 and NBR1, receptor proteins for selective autophagy, together with ubiquitin, accumulated in Atg9a-deficient neurosoma at postnatal d 15 (P15), indicating an inhibition of autophagy, whereas these proteins were significantly decreased at P28, as evidenced by immunohistochemistry, electron microscopy and western blot. Conversely, degenerative changes such as spongiosis of nerve fiber tracts proceeded in axons and their terminals that were occupied with aberrant membrane structures and amorphous materials at P28, although no clear-cut degenerative change was detected in neuronal cell bodies. Different from autophagy, diffusion tensor magnetic resonance imaging and histological observations revealed Atg9a-deficiency-induced dysgenesis of the corpus callosum and anterior commissure. As for the neurite extensions of primary cultured neurons, the neurite outgrowth after 3 d culturing was significantly impaired in primary neurons from atg9a-KO mouse brains, but not in those from atg7-KO and atg16l1-KO brains. Moreover, this tendency was also confirmed in Atg9a-knockdown neurons under an atg7-KO background, indicating the role of ATG9A in the regulation of neurite outgrowth that is independent of autophagy. These results suggest that Atg9a deficiency causes progressive degeneration in the axons and their terminals, but not in neuronal cell bodies, where the degradations of SQSTM1/p62 and NBR1 were insufficiently suppressed. Moreover, the deletion of Atg9a impaired nerve fiber tract formation.
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DOI：
10.1083/jcb.201402054
发表时间：
2014-05-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Okamoto K
通讯作者：
Okamoto K
影响因子：
16
作者：
Kirkin, Vladimir;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
64.8
作者：
Khaminets, Aliaksandr;Heinrich, Theresa;Dikic, Ivan
通讯作者：
Dikic, Ivan
MAP1B 是轴突引导所必需的，并且参与中枢和周围神经系统的发育。
影响因子：
7.8
作者：
Meixner, A;Haverkamp, S;Wässle, H;Führer, S;Thalhammer, J;Kropf, N;Bittner, RE;Lassmann, H;Wiche, G;Propst, F
通讯作者：
Propst, F
p62/SQSTM1形成自噬降解的蛋白质聚集体，并对亨廷顿蛋白诱导的细胞死亡具有保护作用。
影响因子：
7.8
作者：
Bjorkoy, Geir;Lamark, Trond;Brech, Andreas;Outzen, Heidi;Perander, Maria;Overvatn, Aud;Stenmark, Harald;Johansen, Terje
通讯作者：
Johansen, Terje