Olena Abigail F, Rao Mahesh B, Thatcher Elizabeth J, Wu Shu-Yu, Patton James G
Department of Biological Sciences, Vanderbilt University, Nashville, TN.
Dev Biol. 2015 Apr 1;400(1):72-81. doi: 10.1016/j.ydbio.2015.01.016. Epub 2015 Jan 31.
Precise regulation of Notch signaling is essential for normal vertebrate development. Mind bomb (Mib) is a ubiquitin ligase that is required for activation of Notch by Notch׳s ligand, Delta. Sorting Nexin 5 (SNX5) co-localizes with Mib and Delta complexes and has been shown to directly bind to Mib. We show that microRNA-216a (miR-216a) is expressed in the retina during early development and regulates snx5 to precisely regulate Notch signaling. miR-216a and snx5 have complementary expression patterns. Knocking down miR-216a and/or overexpression of snx5 resulted in increased Notch activation. Conversely, knocking down snx5 and/or miR-216a overexpression caused a decrease in Notch activation. We propose a model in which SNX5, precisely controlled by miR-216a, is a vital partner of Mib in promoting endocytosis of Delta and subsequent activation of Notch signaling.
Notch信号的精确调控对于正常脊椎动物发育至关重要。Mind bomb(Mib)是一种泛素连接酶,是Notch的配体Delta激活Notch所必需的。分选连接蛋白5(SNX5)与Mib和Delta复合物共定位,并且已被证明可直接与Mib结合。我们发现,微小RNA-216a(miR-216a)在早期发育过程中在视网膜中表达,并调节snx5以精确调控Notch信号。miR-216a和snx5具有互补的表达模式。敲低miR-216a和/或过表达snx5会导致Notch激活增加。相反,敲低snx5和/或过表达miR-216a会导致Notch激活减少。我们提出了一个模型,其中由miR-216a精确控制的SNX5是Mib在促进Delta内吞作用及随后激活Notch信号方面的重要伙伴。