WAVE facilitates polarized E-cadherin transport.
WAVE facilitates polarized E-cadherin transport.
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DOI：
10.1091/mbc.e22-08-0322
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发表时间：
2023-05-01
影响因子：
3.3
通讯作者：
Soto M
中科院分区：
文献类型：
--
作者：
Cordova-Burgos L;Rao D;Egwuonwu J;Borinskaya S;Sasidharan S;Soto M
钙粘蛋白动力学驱动形态发生，而钙粘蛋白极性的缺陷有助于疾病，包括癌症。然而，极化钙粘蛋白膜分布的力量还没有很好地理解。我们以前表明，波依赖性分支肌动蛋白极化钙粘蛋白分布，并建议，一种机制是蛋白质运输。虽然以前的研究表明，WAVE是丰富的各种内吞细胞器，WAVE在蛋白质运输的作用是研究不足。在这里，我们测试的模型，波调节钙粘蛋白极化其运输。为了支持这一模型，我们表明：1）内源性标记的WAVE在体内积累在几个内吞细胞器，包括再循环内体和高尔基体; 2）同样，钙粘蛋白在再循环内体和高尔基体积累; 3）WAVE组分的损失减少了钙粘蛋白在顶部定向RAB-11阳性再循环内体的积累，并增加了在高尔基体的积累。此外，实时成像表明，在WAVE组分耗尽的动物中，富含RAB-11：：GFP和RFP：：RME-1的再循环内体的动力学和速度降低，并且RAB-11：：GFP运动被错误定向，表明WAVE为它们的运动提供动力和指导。该体内研究证明了WAVE在促进上皮细胞极化转运中的重要性，并支持WAVE通过促进钙粘蛋白转运促进细胞-细胞粘附和极性的模型。
Cadherin dynamics drive morphogenesis, while defects in cadherin polarity contribute to diseases, including cancers. However, the forces polarizing cadherin membrane distribution are not well understood. We previously showed that WAVE-dependent branched actin polarizes cadherin distribution and suggested that one mechanism is protein transport. While previous studies suggested that WAVE is enriched at various endocytic organelles, the role of WAVE in protein traffic is understudied. Here we test the model that WAVE regulates cadherin by polarizing its transport. In support of this model we show that 1) endogenously tagged WAVE accumulates in vivo at several endocytic organelles, including recycling endosomes and at the Golgi; 2) likewise, cadherin protein accumulates at recycling endosomes and the Golgi; 3) loss of WAVE components reduces cadherin accumulation at apically directed RAB-11–positive recycling endosomes and increases accumulation at the Golgi. In addition, live imaging illustrates that dynamics and velocity of recycling endosomes enriched for RAB-11::GFP and RFP::RME-1 are reduced in animals depleted of WAVE components and RAB-11::GFP movements are misdirected, suggesting that WAVE powers and directs their movements. This in vivo study demonstrates the importance of WAVE in promoting polarized transport in epithelia and supports a model that WAVE promotes cell–cell adhesion and polarity by promoting cadherin transport.
影响因子：
21.3
作者：
Anitei, Mihaela;Stange, Christoph;Parshina, Irina;Baust, Thorsten;Schenck, Annette;Raposo, Graca;Kirchhausen, Tomas;Hoflack, Bernard
通讯作者：
Hoflack, Bernard
影响因子：
2.7
作者：
Patel, Falshruti B.;Soto, Martha C.
通讯作者：
Soto, Martha C.
影响因子：
2.7
作者：
Cordova-Burgos L;Patel FB;Soto MC
通讯作者：
Soto MC