An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state

Mikael Egebjerg Pedersen; Goda Snieckute; Konstantinos Kagias; Camilla Nehammer; Hinke A B Multhaupt; John R Couchman; Roger Pocock

doi:10.1126/science.1242528

An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state

Mikael Egebjerg Pedersen, Goda Snieckute, Konstantinos Kagias, Camilla Nehammer, Hinke A B Multhaupt, John R Couchman, Roger Pocock

Nutritional Immunology

59 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Science
Vol/bind	341
Udgave nummer	6152
Sider (fra-til)	1404-8
Antal sider	5
ISSN	0036-8075
DOI	https://doi.org/10.1126/science.1242528
Status	Udgivet - 20 sep. 2013

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10.1126/science.1242528

Citationsformater

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AU - Pedersen, Mikael Egebjerg

AU - Snieckute, Goda

AU - Kagias, Konstantinos

AU - Nehammer, Camilla

AU - Multhaupt, Hinke A B

AU - Couchman, John R

AU - Pocock, Roger

PY - 2013/9/20

Y1 - 2013/9/20

N2 - 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.

AB - 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.

U2 - 10.1126/science.1242528

DO - 10.1126/science.1242528

M3 - Journal article

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An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state

Abstract

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