miR-216a regulates snx5, a novel notch signaling pathway component, during zebrafish retinal development

Dev Biol. 2015 Apr 1;400(1):72-81. doi: 10.1016/j.ydbio.2015.01.016. Epub 2015 Jan 31.

Abstract

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.

Keywords: Notch signaling; Retina; Sorting Nexin 5; Zebrafish; miR-216a; microRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cloning, Molecular
  • DNA Primers / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Knockdown Techniques
  • Image Processing, Computer-Assisted
  • Immunoblotting
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microarray Analysis
  • Models, Biological
  • Receptors, Notch / metabolism
  • Retina / embryology*
  • Retina / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Sorting Nexins / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*
  • Zebrafish / embryology*
  • Zebrafish Proteins / metabolism*

Substances

  • DNA Primers
  • Intracellular Signaling Peptides and Proteins
  • MIRN216 microRNA, zebrafish
  • Membrane Proteins
  • MicroRNAs
  • Receptors, Notch
  • Snx5 protein, zebrafish
  • Sorting Nexins
  • Zebrafish Proteins
  • delta protein
  • Ubiquitin-Protein Ligases
  • mib1 protein, zebrafish