Mdm20 Modulates Actin Remodeling through the mTORC2 Pathway via Its Effect on Rictor Expression
Kunihiko Yasuda1, Mayumi Takahashi1, Nozomu Mori1
1The Department of Anatomy and Neurobiology, Nagasaki University School of Medicine, Nagasaki, Japan.
Plos One
|November 25, 2015
Summary
The Mdm20 subunit of N-terminal acetyltransferase B (NatB) is crucial for mammalian cell growth and motility. Mdm20 regulates Rictor, mTORC2 activity, and downstream signaling pathways impacting the actin cytoskeleton.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- N-terminal acetyltransferase B (NatB) comprises catalytic Nat5 and auxiliary Mdm20 subunits.
- NatB acetylates N-terminal methionines, regulating protein synthesis and actin remodeling via tropomyosin (Trpm) in yeast.
- The functions of Mdm20 and Nat5 in mammalian cells remain largely uncharacterized.
Purpose of the Study:
- To investigate the biological roles of Mdm20 and Nat5 subunits in mammalian cells.
- To elucidate the molecular mechanisms by which Mdm20 influences cell growth, motility, and cytoskeletal organization.
Main Methods:
- Utilized knockdown (KD) models in HEK293 and HeLa cells to assess Mdm20 and Nat5 functions.
- Analyzed cell growth, cellular motility, stress fiber formation, and Trpm localization.
- Investigated the expression of Rictor, an mTORC2 component, and PKCαS657 phosphorylation.
- Examined FoxO1 phosphorylation in response to serum starvation and insulin stimulation.
Main Results:
- Mdm20-KD, but not Nat5-KD, suppressed cell growth and motility.
- Mdm20-KD cells exhibited stress fiber formation, but Trpm localization was disrupted.
- Mdm20 knockdown led to reduced Rictor expression and PKCαS657 phosphorylation.
- Mdm20 regulates FoxO1 phosphorylation via the Mdm20-mTORC2-Akt pathway.
Conclusions:
- Mdm20 is essential for mammalian cell growth and motility.
- Mdm20 functions as a novel regulator of Rictor, controlling mTORC2 activity.
- Mdm20 influences actin cytoskeleton organization through PKCαS657 and FoxO1 signaling.
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