Related Experiment Video
Updated: Jul 8, 2026
14:47
Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
Published on: May 17, 2016
PLD regulates myoblast differentiation through the mTOR-IGF2 pathway.
1Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 S. Goodwin Avenue B107, Urbana, IL 61801, USA.
Journal of Cell Science
|January 17, 2008
Summary
Phospholipase D1 (PLD1) is crucial for skeletal muscle cell differentiation by activating the mTOR-IGF2 pathway. This finding reveals a new mechanism regulating myogenesis and muscle growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The mammalian target of rapamycin (mTOR) pathway regulates skeletal myoblast differentiation.
- Phospholipase D (PLD) is implicated in cell growth and mTOR signaling, but its role in myoblast differentiation is unclear.
Purpose of the Study:
- To investigate the role of PLD in the autocrine regulation of skeletal myoblast differentiation.
- To elucidate the specific PLD isoforms and signaling pathways involved in myogenesis.
Main Methods:
- Upregulation of PLD1 and PLD2 expression during differentiation of mouse C2C12 satellite cells was assessed.
- Inhibition of PLD activity using 1-butanol and gene knockdown of PLD1/PLD2 were employed.
- The involvement of the mTOR pathway, actin cytoskeleton, and IGF2 production was analyzed.
Main Results:
- PLD1 and PLD2 expression increased during C2C12 cell differentiation.
- PLD inhibition or PLD1 knockdown significantly impaired C2C12 differentiation.
- PLD1 positively regulates mTOR signaling, promoting IGF2 production, which is essential for initiating differentiation.
Conclusions:
- PLD1, not PLD2, is critical for skeletal myogenesis.
- PLD1 regulates myoblast differentiation via the mTOR-IGF2 pathway, independent of actin cytoskeleton modulation.
- PLD1-mediated IGF2 production is a key autocrine mechanism initiating satellite cell differentiation.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
01:13Formation of Muscle Fibers from Myoblasts
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...