An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state.
An appropriate balance in glycosylation of proteoglycans is crucial for their ability to regulate animal development. Here, we report that the Caenorhabditis elegans microRNA mir-79, an ortholog of mammalian miR-9, controls sugar-chain homeostasis by targeting two proteins in the proteoglycan biosynthetic pathway: a chondroitin synthase (SQV-5; squashed vulva-5) and a uridine 5'-diphosphate-sugar transporter (SQV-7). Loss of mir-79 causes neurodevelopmental defects through SQV-5 and SQV-7 dysregulation in the epidermis. This results in a partial shutdown of heparan sulfate biosynthesis that impinges on a LON-2/glypican pathway and disrupts neuronal migration. Our results identify a regulatory axis controlled by a conserved microRNA that maintains proteoglycan homeostasis in cells.
Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, Denmark.
Mikael Egebjerg
ME
Pedersen
Goda
G
Snieckute
Konstantinos
K
Kagias
Camilla
C
Nehammer
Hinke A B
HA
Multhaupt
John R
JR
Couchman
Roger
R
Pocock
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D004817:Epidermis / Q000378:metabolism*; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism; D053673:Glypicans / Q000096:biosynthesis / Q000235:genetics; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D033701:Nucleobase, Nucleoside, Nucleotide, and Nucleic Acid Transport Proteins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; C518316:LON-2 protein, C elegans; C583923:MIRN79 microRNA, C elegans; D035683:MicroRNAs; D009004:Monosaccharide Transport Proteins; D033701:Nucleobase, Nucleoside, Nucleotide, and Nucleic Acid Transport Proteins; C414738:sqv-7 protein, C elegans; D016695:Glycosyltransferases; C474582:sqv-5 protein, C elegans