Toll receptors remodel epithelia by directing planar-polarized Src and PI3K activity.
Toll receptors remodel epithelia by directing planar-polarized Src and PI3K activity.
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DOI：
10.1016/j.devcel.2021.04.012
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发表时间：
2021-06-07
影响因子：
11.8
通讯作者：
Zallen JA
中科院分区：
文献类型：
--
作者：
Tamada M;Shi J;Bourdot KS;Supriyatno S;Palmquist KH;Gutierrez-Ruiz OL;Zallen JA
Toll样受体对动物的发育和生存至关重要，在先天免疫、组织模式和细胞行为中具有保守的作用。Toll受体向细胞核发出信号的机制已得到很好的表征，但Toll受体如何在细胞膜上产生快速的局部信号以产生细胞极性和行为的急性变化尚不清楚。我们发现，果蝇Toll受体直接上皮会聚延伸诱导平面极化模式的皮质Src和PI 3-激酶（PI 3 K）的活动。Toll受体将Src活性靶向至膜上的特定位点，并且Src通过Toll-2胞质结构域的酪氨酸磷酸化将PI 3 K募集至Toll-2复合物。降低Src或PI 3 K活性破坏平面极化肌球蛋白组装、细胞嵌入和会聚延伸，而组成性Src活性促进异位PI 3 K和肌球蛋白皮质定位。这些结果表明，Toll受体通过局部动员Src和PI 3 K活性来指导细胞极性和行为。Toll受体提供关键的空间线索，驱动细胞运动在收敛延伸。Tamada和Shi等人表明，Toll受体通过产生Src和PI 3 K活性的平面极化模式来组织细胞运动。Toll-2酪氨酸磷酸化将PI 3 K募集至Toll-2复合物，促进局部肌球蛋白组装和细胞重排。
Toll-like receptors are essential for animal development and survival, with conserved roles in innate immunity, tissue patterning, and cell behavior. The mechanisms by which Toll receptors signal to the nucleus are well characterized, but how Toll receptors generate rapid, localized signals at the cell membrane to produce acute changes in cell polarity and behavior is not known. We show that Drosophila Toll receptors direct epithelial convergent extension by inducing planar polarized patterns of cortical Src and PI3-kinase (PI3K) activity. Toll receptors target Src activity to specific sites at the membrane, and Src recruits PI3K to the Toll-2 complex through tyrosine phosphorylation of the Toll-2 cytoplasmic domain. Reducing Src or PI3K activity disrupts planar polarized myosin assembly, cell intercalation, and convergent extension, whereas constitutive Src activity promotes ectopic PI3K and myosin cortical localization. These results demonstrate that Toll receptors direct cell polarity and behavior by locally mobilizing Src and PI3K activity. Toll receptors provide critical spatial cues that drive cell movements during convergent extension. Tamada and Shi et al. show that Toll receptors organize cell movements by generating planar polarized patterns of Src and PI3K activity. Toll-2 tyrosine phosphorylation recruits PI3K to the Toll-2 complex, promoting localized myosin assembly and cell rearrangement.
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影响因子：
30.5
作者：
Arbibe, L;Mira, JP;Knaus, UG
通讯作者：
Knaus, UG
影响因子：
5.3
作者：
Cameron, Jill S.;Alexopoulou, Lena;Vartanian, Timothy
通讯作者：
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DOI：
10.1126/stke.3772007re2
发表时间：
2007-03-13
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
--
作者：
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通讯作者：
Lowell, Clifford A
影响因子：
4.6
作者：
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通讯作者：
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影响因子：
16.6
作者：
Chen, Dong-Yuan;Crest, Justin;Bilder, David
通讯作者：
Bilder, David