Dystroglycan and perlecan provide a basal cue required for epithelial polarity during energetic stress.

Dystroglycan and perlecan provide a basal cue required for epithelial polarity during energetic stress.
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DOI:
10.1016/j.devcel.2008.11.006
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发表时间:
2009-01
期刊:
影响因子:
11.8
通讯作者:
Ray, Robert P.
Ray, Robert P.
中科院分区:
生物学1区
文献类型:
--
作者:
Mirouse, Vincent;Christoforou, Christina P.;Fritsch, Cornelia;St Johnston, Daniel;Ray, Robert P.

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肌营养不良聚糖定位于上皮细胞的基底结构域,并已报道在顶-基底极性中起作用。在这里,我们表明,Dystroglycan无效突变体卵泡细胞具有正常的顶部-基底极性,但失去了其基底肌动蛋白应力纤维的平面极性,这是一种与Dystrophin突变体共有的表型。然而,与肌营养不良蛋白突变体不同,肌营养不良聚糖或其细胞外基质配体串珠素的突变体在能量应激下失去极性。在能量应激下维持上皮极性需要通过细胞能量传感器AMPK激活肌球蛋白II。饥饿的Dystroglycan或Perlecan无效细胞正常激活AMPK,但不激活肌球蛋白II。因此,通过肌营养不良聚糖的串珠素信号传导可以确定肌球蛋白II可以被AMPK激活的位置,从而为低能上皮极性途径提供基础极性线索。由于肌营养不良聚糖通常在肿瘤中下调,因此该途径的丧失可能在癌症进展中起作用。
Dystroglycan localizes to the basal domain of epithelial cells and has been reported to play a role in apical-basal polarity. Here, we show that Dystroglycan null mutant follicle cells have normal apical-basal polarity, but lose the planar polarity of their basal actin stress fibers, a phenotype it shares with Dystrophin mutants. However, unlike Dystrophin mutants, mutants in Dystroglycan or in its extracellular matrix ligand Perlecan lose polarity under energetic stress. The maintenance of epithelial polarity under energetic stress requires the activation of Myosin II by the cellular energy sensor AMPK. Starved Dystroglycan or Perlecan null cells activate AMPK normally, but do not activate Myosin II. Thus, Perlecan signaling through Dystroglycan may determine where Myosin II can be activated by AMPK, thereby providing the basal polarity cue for the low-energy epithelial polarity pathway. Since Dystroglycan is often downregulated in tumors, loss of this pathway may play a role in cancer progression.
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