Abstract
Dynamin-related protein1 (Drp1) plays an essential role in mitochondrial fission: Cytosolic Drp1 is translocated to the mitochondria upon stimulus, and oligomerized Drp1 constricts mitochondria by aid of actin filaments. Drp1 completes the fission process with GTP hydrolysis by its own GTPase activity. The importance of actin filament and its interaction with Drp1 in the mitochondrial fission process have been demonstrated. In this study, we found that Drp1 is enriched in the actin-rich leading edge of lamellipodia of mouse embryonic fibroblasts (MEFs) wherein mitochondria or peroxisomes are absent. Mff-binding mutant (A395D) of Drp1, which cannot be recruited to mitochondria, was also localized in lamellipodia, indicating that Drp1 in lamellipodia is not related to mitochondria. When lamellipodia formation was induced by platelet-derived growth factor (PDGF) in MEFs, S616 phosphorylated form of Drp1 was accumulated to the lamellipodia. Inhibition of Drp1 with Mdivi-1 or a specific shRNA significantly decreased PDGF-induced lamellipodia formation or initial cell spreading during re-plating of the cells, respectively. Interestingly, defective lamellipodia formation and cell adhesion caused by Drp1 inhibition were not rescued by supplementing L-carnitine, although it restored mitochondrial energy loss caused by Drp1 inhibition. Collectively, these results favor the idea that Drp1 might play a significant role in lamellipodia formation and cell spreading through a different mechanism from that used for regulating mitochondrial dynamics/function.
| Original language | English |
|---|---|
| Pages (from-to) | 13-20 |
| Number of pages | 8 |
| Journal | Histochemistry and Cell Biology |
| Volume | 148 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2017 Jul 1 |
Bibliographical note
Funding Information:This research was supported by the Brain Research Program through the National Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2016R1D1A1B01011346, NRF-2012M3A9C6049933) and by Institute of Human Genetics, Korea University College of Medicine. We thank Dr. Bokkee Eun in Core Laboratory for Convergent Translational Research, College of Medicine, Korea University for helpful discussion.
Publisher Copyright:
© 2017, Springer-Verlag Berlin Heidelberg.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
Keywords
- Actin filaments
- Cell spreading
- Drp1
- Lamellipodia
- PDGF
ASJC Scopus subject areas
- Histology
- Molecular Biology
- Medical Laboratory Technology
- Cell Biology