Role of Phosphatidylinositol 3,4,5-Trisphosphate (PIP3) 5-Phosphatase Skeletal Muscle- and Kidney-enriched Inositol Polyphosphate Phosphatase (SKIP) in Myoblast Differentiation

Ijuin, Takeshi; Takenawa, Tadaomi

doi:10.1074/jbc.m112.388785

Cited by 11 publications

(15 citation statements)

References 35 publications

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“…mTOR activation also suppresses TFEB/TFE3-lysosomal biogenesis (10)(11)(12). It is established from multiple studies that INPP5K (also called SKIP) degrades PI(3,4,5)P3 to suppress AKT/mTOR signalling (40,(53)(54)(55)(56)(57)(58), therefore, we questioned if INPP5K regulation of autophagy was AKTdependent. Consistent with previous reports enhanced AKT/mTOR activation was observed in Figure 6; G-H), but did not alleviate autophagy inhibition (Supplementary Figure 6; I-J) or muscle disease (Supplementary Figure 6; K-N).…”

Section: Inpp5k Does Not Regulate Autophagy Via Akt Signallingmentioning

confidence: 98%

Defective lysosome reformation during autophagy causes skeletal muscle disease

Mcgrath¹,

Eramo²,

Gurung³

et al. 2021

Journal of Clinical Investigation

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The regulation of autophagy-dependent lysosome homeostasis in vivo is unclear. We show the inositol polyphosphate 5-phosphatase INPP5K regulates autophagic lysosome reformation (ALR), a lysosome recycling pathway, in muscle. INPP5K hydrolyses phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) to phosphatidylinositol 4-phosphate (PI(4)P) and INPP5K mutations cause muscular dystrophy by unknown mechanisms. We report loss of INPP5K in muscle causes severe disease, autophagy inhibition and lysosome depletion. Reduced PI(4,5)P2 turnover on autolysosomes in Inpp5k-/muscle suppresses autophagy and lysosome repopulation via ALR inhibition. Defective ALR in Inpp5k-/myoblasts was characterised by enlarged autolysosomes and the persistence of hyperextended reformation tubules, structures that participate in membrane-recycling to form lysosomes. Reduced disengagement of the PI(4,5)P2 effector clathrin was observed on reformation tubules which we propose interferes with ALR completion. Inhibition of PI(4,5)P2 synthesis, or expression of wild-type, but not INPP5K-disease mutants in INPP5K-depleted myoblasts restored lysosomal homeostasis. Therefore, bidirectional interconversion of PI(4)P/PI(4,5)P2 on autolysosomes is integral to lysosome replenishment and autophagy function in muscle. Activation of TFEB-dependent de novo lysosome biogenesis did not compensate for loss of ALR in Inpp5k-/muscle, revealing a dependence on this lysosome recycling pathway. Therefore, in muscle, ALR is indispensable for lysosome homeostasis during autophagy and when defective is associated with muscular dystrophy.

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Section: Inpp5k Does Not Regulate Autophagy Via Akt Signallingmentioning

confidence: 98%

Defective lysosome reformation during autophagy causes skeletal muscle disease

Mcgrath¹,

Eramo²,

Gurung³

et al. 2021

Journal of Clinical Investigation

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“…Expression of INPP5K mRNA and protein increased during C2C12 cell differentiation into myotubes. In addition, MyoD, a transcription factor essential for myoblast specification during embryogenesis and in adults, induced INPP5K mRNA expression in these cells, partly via cis-acting elements in the INPP5K promoter (Xiong et al, 2011;Ijuin and Takenawa, 2012a). C2C12 cell differentiation into myotubes was decreased when INPP5K was overexpressed and, inversely, endogenous INPP5K silencing was associated with increased myotubes formation.…”

Section: Myoblasts Differentiation and Control Of The Igf-ii Autocrinmentioning

confidence: 99%

“…In the proposed model, INPP5K dephosphorylates PtdIns(3,4,5)P3 in the IGF-II signaling pathway, leading to decreased AKT/mTOR phosphorylation and IGF-II mRNA and protein production, acting thus as a brake on this positive autocrine loop. This mechanism could explain why INPP5K overexpression in C2C12 cells decreased myoblast differentiation and why decreased endogenous INPP5K expression in these cells and in INPP5K gene-modified Pps Brdm1/+ heterozygous mice led to significantly increased differentiation into myotubes and quadriceps muscle weight compared to controls (Ijuin et al, 2008(Ijuin et al, , 2012a.…”

Section: Myoblasts Differentiation and Control Of The Igf-ii Autocrinmentioning

confidence: 99%

“…Physiological and physiopathological conditions associated with an increased INPP5K mRNA/protein expression include skeletal muscle cell differentiation (Xiong et al, 2011;Ijuin and Takenawa, 2012a), endoplasmic reticulum stress and activation of the unfold protein response (Ijuin et al, 2015a) as well as insulin resistance, obesity and diabetes (Ijuin et al, 2015a). In cancer, INPP5K mRNA expression was found either significantly increased (endometrial carcinoma (Hedberg Oldfors et al, 2015), prostate cancer (Flaig et al, 2017), glioblastoma (Davies et al, 2015), renal cancer (Jones et al, 2005)) or decreased (lung adenocarcinoma (Gao et al, 2017), glioblastoma (Davies et al, 2015)), depending on the cancer cell type.…”

Section: Expression Of Inpp5k Mrnas and Proteins In Human And Mouse Tmentioning

confidence: 99%

“…C2C12 cell differentiation into myotubes was decreased when INPP5K was overexpressed and, inversely, endogenous INPP5K silencing was associated with increased myotubes formation. A model was proposed by Ijuin and colleagues where INPP5K controls the IGF-II autocrine regulatory loop and thus myoblast differentiation (Ijuin and Takenawa, 2012a). Indeed, during myoblast differentiation, IGF-II up-regulates its own gene expression through the PI3kinase/PtdIns(3,4,5)P3/AKT/mTOR signaling pathway, leading to IGF-II production and secretion in the extracellular space.…”

Section: Myoblasts Differentiation and Control Of The Igf-ii Autocrinmentioning

confidence: 99%

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The phosphoinositide 5-phosphatase INPP5K: From gene structure to in vivo functions

Schurmans

Catsyne

Desmet

et al. 2021

Advances in Biological Regulation

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INPP5K (Inositol Polyphosphate 5-Phosphatase K, or SKIP (for Skeletal muscle and Kidney enriched Inositol Phosphatase) is a member of the phosphoinositide 5-phosphatases family. Its protein structure is comprised of a N-terminal catalytic domain which hydrolyses both PtdIns(4,5)P2 and PtdIns(3,4,5)P3, followed by a SKICH domain at the C-terminus which is responsible for protein-protein interactions and subcellular localization of INPP5K. Strikingly, INPP5K is mostly concentrated in the endoplasmic reticulum, although it is also detected at the plasma membrane, in the cytosol and the nucleus. Recently, mutations in INPP5K have been detected in patients with a rare form of autosomal recessive congenital muscular dystrophy with cataract, short stature and intellectual disability. INPP5K functions extend from control of insulin signaling, endoplasmic reticulum stress response and structural integrity, myoblast differentiation, cytoskeleton organization, cell adhesion and migration, renal osmoregulation, to cancer. The goal of this review is thus to summarize and comment recent and less recent data in the literature on INPP5K, in particular on the structure, expression, intracellular localization, interactions and functions of this specific member of the 5-phosphatases family.

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Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways

Zanou

Gailly

2013

Cell. Mol. Life Sci.

267

208

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Adult skeletal muscle can regenerate in response to muscle damage. This ability is conferred by the presence of myogenic stem cells called satellite cells. In response to stimuli such as injury or exercise, these cells become activated and express myogenic regulatory factors (MRFs), i.e., transcription factors of the myogenic lineage including Myf5, MyoD, myogenin, and Mrf4 to proliferate and differentiate into myofibers. The MRF family of proteins controls the transcription of important muscle-specific proteins such as myosin heavy chain and muscle creatine kinase. Different growth factors are secreted during muscle repair among which insulin-like growth factors (IGFs) are the only ones that promote both muscle cell proliferation and differentiation and that play a key role in muscle regeneration and hypertrophy. Different isoforms of IGFs are expressed during muscle repair: IGF-IEa, IGF-IEb, or IGF-IEc (also known as mechano growth factor, MGF) and IGF-II. MGF is expressed first and is observed in satellite cells and in proliferating myoblasts whereas IGF-Ia and IGF-II expression occurs at the state of muscle fiber formation. Interestingly, several studies report the induction of MRFs in response to IGFs stimulation. Inversely, IGFs expression may also be regulated by MRFs. Various mechanisms are proposed to support these interactions. In this review, we describe the general process of muscle hypertrophy and regeneration and decipher the interactions between the two groups of factors involved in the process.

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Role of Phosphatidylinositol 3,4,5-Trisphosphate (PIP3) 5-Phosphatase Skeletal Muscle- and Kidney-enriched Inositol Polyphosphate Phosphatase (SKIP) in Myoblast Differentiation

Cited by 11 publications

References 35 publications

Defective lysosome reformation during autophagy causes skeletal muscle disease

Defective lysosome reformation during autophagy causes skeletal muscle disease

The phosphoinositide 5-phosphatase INPP5K: From gene structure to in vivo functions

Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways

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