de Groot Reinoud E A, Rappel Sophia B, Lorenowicz Magdalena J, Korswagen Hendrik C
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
Cell Signal. 2014 Dec;26(12):2601-5. doi: 10.1016/j.cellsig.2014.08.016. Epub 2014 Aug 27.
Wnt proteins are lipid modified signaling molecules that have essential functions in development and adult tissue homeostasis. Secretion of Wnt is mediated by the transmembrane protein Wntless, which binds Wnt and transports it from the endoplasmic reticulum to the cell surface for release. To maintain efficient Wnt secretion, Wntless is recycled back to the Golgi and the endoplasmic reticulum through endocytosis and retromer dependent endosome to Golgi transport. We have previously identified protein kinase CK2 (CK2) in a genome-wide screen for regulators of Wnt signaling in Caenorhabditis elegans. Here, we show that CK2 function is required in Wnt producing cells for Wnt secretion. This function is evolutionarily conserved, as inhibition of CK2 activity interferes with Wnt5a secretion from mammalian cells. Mechanistically, we show that inhibition of CK2 function results in enhanced plasma membrane localization of Wls in C. elegans and mammalian cells, consistent with the notion that CK2 is involved in the regulation of Wls internalization.
Wnt蛋白是脂质修饰的信号分子，在发育和成年组织稳态中具有重要功能。Wnt的分泌由跨膜蛋白Wntless介导，Wntless结合Wnt并将其从内质网转运到细胞表面以释放。为了维持高效的Wnt分泌，Wntless通过内吞作用和依赖于回收蛋白的内体到高尔基体的转运循环回到高尔基体和内质网。我们之前在全基因组筛选中鉴定出蛋白激酶CK2（CK2）是秀丽隐杆线虫Wnt信号通路调节剂。在这里，我们表明Wnt产生细胞中Wnt分泌需要CK2功能。这种功能在进化上是保守的，因为抑制CK2活性会干扰哺乳动物细胞中Wnt5a的分泌。从机制上讲，我们表明抑制CK2功能会导致秀丽隐杆线虫和哺乳动物细胞中Wls在质膜上的定位增强，这与CK2参与Wls内化调节的观点一致。
