CtBP1/BARS is an activator of phospholipase D1 necessary for agonist-induced macropinocytosis

• Published in: The EMBO journal Vol. 28; no. 9; pp. 1197 - 1207
• Main Authors: Haga, Yuki, Miwa, Noriko, Jahangeer, Saleem, Okada, Taro, Nakamura, Shun-ichi
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 06.05.2009; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Adenosine diphosphate; Animals; Biochemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Carrier Proteins - physiology; Cellular biology; Cercopithecus aethiops; COS Cells; CtBP1/BARS; Epidermal Growth Factor - pharmacology; Humans; Immunoprecipitation; Lipids; macropinocytosis; Molecular biology; phospholipase D; Phospholipase D - genetics; Phospholipase D - metabolism; Physiology; Pinocytosis - drug effects; Protein Binding; Proteins; Rats; RNA, Small Interfering - genetics; RNA, Small Interfering - physiology; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2009.78

Vesicular trafficking such as macropinocytosis is a dynamic process that requires coordinated interactions between specialized proteins and lipids. A recent report suggests the involvement of CtBP1/BARS in epidermal growth factor (EGF)‐induced macropinocytosis. Detailed mechanisms as to how lipid remodelling is regulated during macropinocytosis are still undefined. Here, we show that CtBP1/BARS is a physiological activator of PLD1 required in agonist‐induced macropinocytosis. EGF‐induced macropinocytosis was specifically blocked by 1‐butanol but not by 2‐butanol. In addition, stimulation of cells by serum or EGF resulted in the association of CtBP1/BARS with PLD1. Finally, CtBP1/BARS activated PLD1 in a synergistic manner with other PLD activators, including ADP‐ribosylation factors as demonstrated by in vitro and intact cell systems. The present results shed light on the molecular basis of how the ‘fission protein’ CtBP1/BARS controls vesicular trafficking events including macropinocytosis.