Localization of dynamin-related protein 1 and its potential role in lamellipodia formation.
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.
Department of Anatomy, Brain Korea 21, Korea University College of Medicine, Anam-Dong, Sungbuk-Gu, Seoul, 136-705, Korea.
Youhwa
Y
Jo
Department of Anatomy, Brain Korea 21, Korea University College of Medicine, Anam-Dong, Sungbuk-Gu, Seoul, 136-705, Korea.
Hyo Min
HM
Cho
Department of Anatomy, Brain Korea 21, Korea University College of Medicine, Anam-Dong, Sungbuk-Gu, Seoul, 136-705, Korea. woongsun@korea.ac.kr.
Woong
W
Sun
Department of Anatomy, Brain Korea 21, Korea University College of Medicine, Anam-Dong, Sungbuk-Gu, Seoul, 136-705, Korea. jaeryunryu@gmail.com.
Jae Ryun
JR
Ryu
D000199:Actins / Q000378:metabolism; D000818:Animals; D034281:Dynamins / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011554:Pseudopodia / Q000378:metabolism*
D000199:Actins; C486391:Dnm1l protein, mouse; D034281:Dynamins
Actin filaments; Cell spreading; Drp1; Lamellipodia; PDGF