PLD regulates myoblast differentiation through the mTOR-IGF2 pathway
Abstract
A mammalian target of rapamycin (mTOR) pathway is essential for the differentiation of cultured skeletal myoblasts in response to growth factor withdrawal. Previously, phospholipase D (PLD) has been found to play a role in cell growth regulation and mitogenic activation of mTOR signaling. However, a role for PLD in the autocrine regulation of myoblast differentiation is not known. Here we show that upon induction of differentiation in mouse C2C12 satellite cells, the expression of both PLD1 and PLD2 is upregulated. C2C12 differentiation is markedly inhibited by 1-butanol, an inhibitor of the PLD-catalyzed transphosphatidylation reaction, and also by the knockdown of PLD1, but not PLD2. Further investigation has revealed that PLD1 is unlikely to regulate myogenesis through modulation of the actin cytoskeleton as previously suggested. Instead, PLD1 positively regulates mTOR signaling leading to the production of IGF2, an autocrine factor instrumental for the initiation of satellite cell differentiation. Furthermore, exogenous IGF2 fully rescues the differentiation defect resulting from PLD1 knockdown. Hence, PLD1 is critically involved in skeletal myogenesis by regulating the mTOR-IGF2 pathway.
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Both IGF1 and IGF2 regulate skeletal muscle development and adult muscle regeneration and hypertrophy.
“Both IGF1 and IGF2 regulate skeletal muscle development and adult muscle regeneration and hypertrophy [10]”
From Apigenin Enhances Skeletal Muscle Hypertrophy and Myoblast Differentiation by Regulating Prmt7 (2017) · cites this paper as [10]
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InfluentialHuman Phospholipase D Activity Transiently Regulates Pyrimidine Biosynthesis in Malignant Gliomas
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“One of the main positive regulators of muscle growth is insulin-like growth factor 1 (IGF-1), which induces an increase in muscle mass by stimulating the Akt pathways [9].”
BackgroundFlt3L is a novel regulator of skeletal myogenesis
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“Lentivirus packaging was performed as previously described (Yoon and Chen, 2008).”
MethodProtein Kinase D2 Is an Essential Regulator of Murine Myoblast Differentiation
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“In addition to myogenic transcription factors, several protein kinases including p38-MAPK [7], PLD [8] and PKC”
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“, 2001), other studies suggested that it has prodifferentiation roles (Nakashima and Nozawa, 1999; Klein, 2005; Yoon and Chen, 2008).”
BackgroundTargeting PTEN to regulate autophagy and promote the repair of injured neurons
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Functional Study of Long Noncoding RNA H19 in Muscle and Liver
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“…isoforms of PLD1 and PLD2, has long been implicated in the regulation of cell growth and proliferation, and has been reported to play important roles in cytoskeletal organization, vesicular trafficking, metabolic regulation, proliferation, and phagocytosis (Hwang et al. 2021 ; Yoon and Chen 2008).”
- Authors
- Yoon, M.-S., & Chen, J.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Chen, Jie
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2008-02-01
- Volume
- 121
- Issue
- 3
- Pages
- 282-289
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1971733850
- Cited by
- 67
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 8 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 8 · 2012: 3
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 48914)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- phospholipase D, phospholipase D1, phospholipase D2, myogenesis, mTOR signaling, insulin-like growth factor II, autocrine regulation, satellite cells, skeletal myogenesis, C2C12 myoblasts, n-butanol, actin cytoskeleton
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Cell Line, Insulin-Like Growth Factor II, Models, Biological, Phospholipase D, Protein Kinases, Signal Transduction, DNA Primers, 1-Butanol, Muscle Development, Myoblasts, Skeletal, RNA Interference, Mice, TOR Serine-Threonine Kinases
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