Auxilin regulates intestinal stem cell proliferation through EGFR.
Auxilin regulates intestinal stem cell proliferation through EGFR.
复制标题
DOI：
10.1016/j.stemcr.2022.03.010
复制
发表时间：
2022-05-10
影响因子：
5.9
通讯作者：
Li, Zhouhua
中科院分区：
文献类型：
--
作者：
Zhao, Hang;Ren, Xuejing;Kong, Ruiyan;Shi, Lin;Li, Zhengran;Wang, Runqi;Ma, Rui;Zhao, Huiqing;Liu, Fuli;Chang, Henry C.;Chen, Chun-Hong;Li, Zhouhua
成体组织的稳态由驻留干细胞维持。成体干细胞的增殖和分化必须紧密平衡，以避免过度增殖或过早分化。然而，如何适当地控制干细胞增殖仍然是难以捉摸的。在这里，我们发现，生长素（Aux）限制肠干细胞（ISC）增殖主要通过EGFR信号。aux缺失导致过度的ISC增殖和中肠稳态破坏，这不太可能由缺陷的Notch信号传导引起。Aux在多种类型的肠细胞中表达。有趣的是，aux耗竭导致EGFR信号传导的显著增加，EGFR在质膜上的强烈积累和EGFR配体响应于组织应激的表达增加。此外，Aux与EGFR共定位和缔合。最后，阻断EGFR信号传导完全抑制了由aux耗尽引起的缺陷。总之，这些数据表明，Aux主要保护EGFR活化，以保持适当的ISC增殖速率，从而维持中肠稳态。Aux保护ISC免于快速增殖以维持肠内稳态在没有aux的情况下Notch信号传导不受影响EGFR信号传导在aux耗尽时异位激活Aux与EGFR缔合并介导其从质膜的清除在这篇文章中，Zhou及其同事表明，生长素主要通过EGFR信号传导限制肠干细胞（ISC）增殖。祖细胞中的aux缺失通过增加EGFR信号传导和增加EGFR配体的表达破坏肠内稳态。Aux与EGFR结合并介导其从质膜上清除以抑制ISC增殖，从而在生理条件下维持肠内稳态。
Adult tissue homeostasis is maintained by residential stem cells. The proliferation and differentiation of adult stem cells must be tightly balanced to avoid excessive proliferation or premature differentiation. However, how stem cell proliferation is properly controlled remains elusive. Here, we find that auxilin (Aux) restricts intestinal stem cell (ISC) proliferation mainly through EGFR signaling. aux depletion leads to excessive ISC proliferation and midgut homeostasis disruption, which is unlikely caused by defective Notch signaling. Aux is expressed in multiple types of intestinal cells. Interestingly, aux depletion causes a dramatic increase in EGFR signaling, with a strong accumulation of EGFR at the plasma membrane and an increased expression of EGFR ligands in response to tissue stress. Furthermore, Aux co-localizes and associates with EGFR. Finally, blocking EGFR signaling completely suppresses the defects caused by aux depletion. Together, these data demonstrate that Aux mainly safeguards EGFR activation to keep a proper ISC proliferation rate to maintain midgut homeostasis. Aux safeguards ISCs from rapid proliferation to maintain intestinal homeostasis Notch signaling is unaffected in the absence of aux EGFR signaling is ectopically activated upon aux depletion Aux associates with EGFR and mediates its clearance from the plasma membrane In this article, Zhou and colleagues show that auxilin restricts intestinal stem cell (ISC) proliferation mainly through EGFR signaling. aux depletion in progenitors disrupts intestinal homeostasis by increased EGFR signaling and increased expression of EGFR ligands. Aux associates with EGFR and mediates its clearance from the plasma membrane to restrain ISC proliferation, thereby maintaining intestinal homeostasis under physiological conditions.
登录
查看更多内容
影响因子：
3.3
作者：
Ding J;Segarra VA;Chen S;Cai H;Lemmon SK;Ferro-Novick S
通讯作者：
Ferro-Novick S
影响因子：
2.9
作者：
Barouch, W;Prasad, K;Eisenberg, E
通讯作者：
Eisenberg, E
DOI：
10.1007/978-3-319-96704-2_9
发表时间：
2018-01-01
期刊：
ENDOCYTOSIS AND SIGNALING
影响因子：
--
作者：
Caldieri, Giusi;Malabarba, Maria Grazia;Sigismund, Sara
通讯作者：
Sigismund, Sara
影响因子：
7.5
作者：
Gervais, Louis;Bardin, Allison J.
通讯作者：
Bardin, Allison J.
网格蛋白结合基序和果蝇辅助蛋白的J-域对于促进凹口配体内吞作用至关重要。
影响因子：
--
作者：
Kandachar, Vasundhara;Bai, Ting;Chang, Henry C.
通讯作者：
Chang, Henry C.