TY - JOUR
T1 - A role for the metalloprotease invadolysin in insulin signaling and adipogenesis
AU - Chang, Ching-Wen
AU - Abhinav, Kanishk
AU - Di Cara, Francesca
AU - Panagakou, Ioanna
AU - Vass, Sharron
AU - Heck, Margarete M.S.
PY - 2016/12/21
Y1 - 2016/12/21
N2 - 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 localisation of invadolysin. The level of invadolysin increased during both murine 3T3-L1 and human SGBS adipogenesis. Invadolysin displayed a dynamic localisation 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.
AB - 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 localisation of invadolysin. The level of invadolysin increased during both murine 3T3-L1 and human SGBS adipogenesis. Invadolysin displayed a dynamic localisation 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.
U2 - 10.1515/hsz-2016-0226
DO - 10.1515/hsz-2016-0226
M3 - Article
C2 - 27622830
SN - 1431-6730
JO - Biological Chemistry
JF - Biological Chemistry
ER -