A juxtamembrane basolateral targeting motif regulates signaling through a TGF-β pathway receptor in Drosophila.
A juxtamembrane basolateral targeting motif regulates signaling through a TGF-β pathway receptor in Drosophila.
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DOI：
10.1371/journal.pbio.3001660
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发表时间：
2022-05
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
在极化上皮细胞中，受体-配体的相互作用可能受到两种相互作用组分的不同空间分布的限制，从而产生了一层未被充分认识的调节复杂性。我们探索了这种调节是否发生在果蝇翼盘中，翼盘是一种上皮组织，TGF-β家族成员Decapentaplegic （Dpp）作为控制生长和模式的形态因子。Dpp蛋白在椎间盘柱状细胞层的细胞外梯度中被观察到，但在椎间盘腔中也均匀存在，这导致了一个问题，即在面对2个明显定位的配体池时，如何实现梯度信号传导。我们发现Dpp II型受体Punt在基底外侧膜富集，而在连接处和根尖表面缺失，而I型受体Tkv则没有。第二种II型受体Wit表现出明显不同的行为，在所有膜区域都检测到该蛋白，但在顶端侧富集。突变研究发现，在翼盘和哺乳动物Madin-Darby犬肾（MDCK）细胞中，Punt的基底外侧限制需要一个短的近膜序列。这种基底外侧靶向（BLT）决定因素可以主要赋予基底外侧定位在其他顶端受体。在靶向基序中改变转基因的punt突变体的拯救表明，由于缺乏功能性BLT而表达apalized punt的果蝇表现出发育缺陷、雌性不育和显著的致死率。我们还表明，尖化的Punt不会产生异位信号，这表明即使在有Punt的情况下，Dpp的尖池也不是一个重要的信号来源。相反，我们发现基底外侧的呈递是最佳信号所必需的。最后，我们提出的证据表明，BLT通过极化分选机制，不同类型的上皮不同。这提示了一种编码，即每种上皮细胞类型可能以不同的方式传输共同受体，从而对空间定位的细胞外配体池产生不同的反应。受体-配体的相互作用可能受到两种相互作用组分的不同空间分布的限制，从而产生了未被充分认识的调控复杂性。这项研究揭示了一种进化保守的跨膜受体（Dpp II型受体Punt）极化传递机制，支持模型上皮组织果蝇翅盘中强大的形态因子信号传导。
In polarized epithelial cells, receptor–ligand interactions can be restricted by different spatial distributions of the 2 interacting components, giving rise to an underappreciated layer of regulatory complexity. We explored whether such regulation occurs in the Drosophila wing disc, an epithelial tissue featuring the TGF-β family member Decapentaplegic (Dpp) as a morphogen controlling growth and patterning. Dpp protein has been observed in an extracellular gradient within the columnar cell layer of the disc, but also uniformly in the disc lumen, leading to the question of how graded signaling is achieved in the face of 2 distinctly localized ligand pools. We find the Dpp Type II receptor Punt, but not the Type I receptor Tkv, is enriched at the basolateral membrane and depleted at the junctions and apical surface. Wit, a second Type II receptor, shows a markedly different behavior, with the protein detected on all membrane regions but enriched at the apical side. Mutational studies identified a short juxtamembrane sequence required for basolateral restriction of Punt in both wing discs and mammalian Madin-Darby canine kidney (MDCK) cells. This basolateral targeting (BLT) determinant can dominantly confer basolateral localization on an otherwise apical receptor. Rescue of punt mutants with transgenes altered in the targeting motif showed that flies expressing apicalized Punt due to the lack of a functional BLT displayed developmental defects, female sterility, and significant lethality. We also show that apicalized Punt does not produce an ectopic signal, indicating that the apical pool of Dpp is not a significant signaling source even when presented with Punt. Instead, we find that basolateral presentation of Punt is required for optimal signaling. Finally, we present evidence that the BLT acts through polarized sorting machinery that differs between types of epithelia. This suggests a code whereby each epithelial cell type may differentially traffic common receptors to enable distinctive responses to spatially localized pools of extracellular ligands. Receptor-ligand interactions can be restricted by different spatial distributions of the two interacting components, giving rise to an underappreciated layer of regulatory complexity. This study reveals that an evolutionarily conserved mechanism for polarized delivery of a transmembrane receptor (the Dpp Type II receptor Punt) supports robust morphogen signaling in a model epithelial tissue, the Drosophila wing disc.
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影响因子：
3.3
作者：
Brunner, Patrizia;Hastar, Nurcan;Knaus, Petra
通讯作者：
Knaus, Petra
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1083/jcb.201310021
发表时间：
2014-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bonifacino JS
通讯作者：
Bonifacino JS
影响因子：
11.8
作者：
Gravotta, Diego;Carvajal-Gonzalez, Jose Maria;Mattera, Rafael;Deborde, Sylvie;Banfelder, Jason R.;Bonifacino, Juan S.;Rodriguez-Boulan, Enrique
通讯作者：
Rodriguez-Boulan, Enrique
影响因子：
64.5
作者：
Entchev, EV;Schwabedissen, A;González-Gaitán, M
通讯作者：
González-Gaitán, M