Rab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control.

Rab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control.
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DOI:
10.1038/ncomms2347
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发表时间:
2013
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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在发育过程中,顶端细胞外基质填充管腔控制上皮管的形态和几何形状,但管腔蛋白组成的调节及其在管腔形态发生中的作用尚不清楚。在这里,我们展示了一种由Rab9、逆聚体和肌动蛋白核心剂WASH(Wiskott-Aldrich综合征蛋白和SCAR Homolog)组成的内体修复机制,调节果蝇气管中管腔蛋白蛇纹石的选择性回收。分泌的蛇纹石被内吞并分选到晚期的内吞体内。VPS35、WASH和肌动蛋白细丝不同地定位于内体膜上富含Rab9的亚区,其中含有蛇纹石的囊泡发芽。在Rab9、VPS35和WASH突变体中,蛇纹石正常分泌到管腔内,但管腔数量在后期耗尽,导致管子过度拉长。相反,许多管腔蛋白的分泌没有受到影响,这表明特定类型的管腔蛋白的逆行运输是持续管长调节的关键限速机制。生物管的发育受细胞和腔外基质相互作用的调控。董等人的研究成果。研究表明,腔内几丁质脱乙酰酶的逆行循环通过限制长度与直径无关来调节果蝇的气管小管几何形状。
Apical extracellular matrix filling the lumen controls the morphology and geometry of epithelial tubes during development, yet the regulation of luminal protein composition and its role in tube morphogenesis are not well understood. Here we show that an endosomal-retrieval machinery consisting of Rab9, retromer and actin nucleator WASH (Wiskott–Aldrich Syndrome Protein and SCAR Homolog) regulates selective recycling of the luminal protein Serpentine in the Drosophila trachea. Secreted Serpentine is endocytosed and sorted into the late endosome. Vps35, WASH and actin filaments differentially localize at the Rab9-enriched subdomains of the endosomal membrane, where Serpentine containing vesicles bud off. In Rab9, Vps35 and WASH mutants, Serpentine was secreted normally into the tracheal lumen, but the luminal quantities were depleted at later stages, resulting in excessively elongated tubes. In contrast, secretion of many luminal proteins was unaffected, suggesting that retrograde trafficking of a specific class of luminal proteins is a pivotal rate-limiting mechanism for continuous tube length regulation. The development of biological tubes is regulated by mutual interactions between cells and luminal extracellular matrix. Dong et al. show that retrograde recycling of luminal chitin deacetylase regulates Drosophila tracheal tubule geometry by restricting length independently of diameter.
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