A role for the metalloprotease invadolysin in insulin signaling and adipogenesis.

Abstract:

:Invadolysin is a novel metalloprotease conserved amongst metazoans that is essential for life in Drosophila. We previously showed that invadolysin was essential for the cell cycle and cell migration, linking to metabolism through a role in lipid storage and interaction with mitochondrial proteins. In this study we demonstrate that invadolysin mutants exhibit increased autophagy and decreased glycogen storage - suggestive of a role for invadolysin in insulin signaling in Drosophila. Consistent with this, effectors of insulin signaling were decreased in invadolysin mutants. In addition, we discovered that invadolysin was deposited on newly synthesized lipid droplets in a PKC-dependent manner. We examined two in vitro models of adipogenesis for the expression and localization of invadolysin. The level of invadolysin increased during both murine 3T3-L1 and human Simpson-Golabi-Behmel syndrome (SGBS), adipogenesis. Invadolysin displayed a dynamic localization to lipid droplets over the course of adipogenesis, which may be due to the differential expression of distinct invadolysin variants. Pharmacological inhibition of adipogenesis abrogated the increase in invadolysin. In summary, our results on in vivo and in vitro systems highlight an important role for invadolysin in insulin signaling and adipogenesis.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Chang CW,Abhinav K,Di Cara F,Panagakou I,Vass S,Heck MM

doi

10.1515/hsz-2016-0226

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

373-393

issue

3

eissn

1431-6730

issn

1437-4315

pii

/j/bchm.2017.398.issue-3/hsz-2016-0226/hsz-2016-02

journal_volume

398

pub_type

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