Type I Phosphotidylinosotol 4-Phosphate 5-Kinase γ Regulates Osteoclasts in a Bifunctional Manner*

Zhu, Tingting; Chappel, Jean; Hsu, Fong‐Fu; Turk, John; Aurora, Rajeev; Hyrc, Krzysztof L.; Camilli, Pietro De; Broekelmann, Thomas J.; Mecham, Robert P.; Teitelbaum, Steven L.; Zou, Wei

doi:10.1074/jbc.m112.446054

Cited by 8 publications

(5 citation statements)

References 29 publications

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“…In addition, PLD1- and PLD2-generated PA is reported to activate and directly regulate PIP5K activity 38,93,94 , and PLD2 can recruit PIP5K to the membrane 95 . Finally, PIP5K has been show to localize at podosome rings in osteoclasts 96 . Since our data show that both PLD1 and PLD2, albeit with some differences, promote podosome formation in a non-redundant concurrent manner (Fig.…”

Section: Discussionmentioning

confidence: 98%

PLD-dependent phosphatidic acid microdomains are signaling platforms for podosome formation

Bolomini-Vittori

Mennens

Joosten

et al. 2019

Sci Rep

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Local membrane phospholipid enrichment serves as docking platform for signaling proteins involved in many processes including cell adhesion and migration. Tissue-resident dendritic cells (DCs) assemble actomyosin-based structures called podosomes, which mediate adhesion and degradation of extracellular matrix for migration and antigen sampling. Recent evidence suggested the involvement of phospholipase D (PLD) and its product phosphatidic acid (PA) in podosome formation, but the spatiotemporal control of this process is poorly characterized. Here we determined the role of PLD1 and PLD2 isoforms in regulating podosome formation and dynamics in human primary DCs by combining PLD pharmacological inhibition with a fluorescent PA sensor and fluorescence microscopy. We found that ongoing PLD2 activity is required for the maintenance of podosomes, whereas both PLD1 and PLD2 control the early stages of podosome assembly. Furthermore, we captured the formation of PA microdomains accumulating at the membrane cytoplasmic leaflet of living DCs, in dynamic coordination with nascent podosome actin cores. Finally, we show that both PLD1 and PLD2 activity are important for podosome-mediated matrix degradation. Our results provide novel insight into the isoform-specific spatiotemporal regulation of PLD activity and further our understanding of the role of cell membrane phospholipids in controlling localized actin polymerization and cell protrusion.

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Section: Discussionmentioning

confidence: 98%

PLD-dependent phosphatidic acid microdomains are signaling platforms for podosome formation

Bolomini-Vittori

Mennens

Joosten

et al. 2019

Sci Rep

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“…Type I Phosphotidylinosotol 4-Phosphate 5-Kinase (PIP5KI) has three isoforms, α, β, and γ. The PIP5KI γ highly abundant in brain and plays important role in cytoskeletal organization [42,43]. SAM50 and TOM70, are…”

Section: Discussionmentioning

confidence: 99%

The role of circadian rhythm in the regulation of cellular protein profiles in the brain

Beker¹,

Kılıç²

2021

Turk J Med Sci

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Background/aim: Circadian rhythm plays a significant role in the regulation of almost all kinds of physiological processes. Besides this it may also have a direct or indirect effect on the neurodegenerative processes, including Alzheimer's disease, Parkinson's disease, and ischemic stroke. Therefore, the identification of circadian rhythm related proteins is crucial to be able to understand the molecular mechanism of the circadian rhythm and to define new therapeutic target for the treatment of degenerative disorders. Materials and methods: To identify the light and dark regulated proteins, 8-12 weeks, male Balb/C mice were used at two different time points (Morning (Zeitgeber time-0 (ZT0)) and midnight (ZT18)) under physiological conditions. Therefore, brain tissues were analyzed via liquid chromatography tandem-mass spectrometry. Results: A totally of 1621 different proteins were identified between ZT0 and ZT18 mice. Among these proteins, 23 proteins were differentially expressed (p<0.05 and fold change 1.4) in ZT18 mice, 11 upregulated (AKAP10,

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“…Xu and colleagues have reported that the polarization of Pip5k1c induced by integrins is required for the recruitment of neutrophils during inflammatory responses [20]. Zhu et al have reported that excessive Pip5k1c expression impairs osteoclast formation and bone resorption via enhancing the Pip2 generation [24]. Our previous study has demonstrated an essential role of Pip5k1c, through its expression in mesenchymal stem cells (MSCs), in the control of bone remodeling [25].…”

mentioning

confidence: 90%

Pip5k1c Loss in Chondrocytes Causes Spontaneous Osteoarthritic Lesions in Aged Mice

Qu¹,

Chen²,

Gong³

et al. 2022

Aging and disease

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Osteoarthritis (OA) is the most common degenerative joint disease affecting the older populations globally. Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (Pip5k1c), a lipid kinase catalyzing the synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), is involved in various cellular processes, such as focal adhesion (FA) formation, cell migration, and cellular signal transduction. However, whether Pip5k1c plays a role in the pathogenesis of OA remains unclear. Here we show that inducible deletion of Pip5k1c in aggrecan-expressing chondrocytes (cKO) causes multiple spontaneous OA-like lesions, including cartilage degradation, surface fissures, subchondral sclerosis, meniscus deformation, synovial hyperplasia, and osteophyte formation in aged (15-month-old) mice, but not in adult (7-month-old) mice. Pip5k1c loss promotes extracellular matrix (ECM) degradation, chondrocyte hypertrophy and apoptosis, and inhibits chondrocyte proliferation in the articular cartilage of aged mice. Pip5k1c loss dramatically downregulates the expressions of several key FA proteins, including activated integrin β1, talin, and vinculin, and thus impairs the chondrocyte adhesion and spreading on ECM. Collectively, these findings suggest that Pip5k1c expression in chondrocytes plays a critical role in maintaining articular cartilage homeostasis and protecting against age-related OA.

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Type I Phosphotidylinosotol 4-Phosphate 5-Kinase γ Regulates Osteoclasts in a Bifunctional Manner*

Cited by 8 publications

References 29 publications

PLD-dependent phosphatidic acid microdomains are signaling platforms for podosome formation

PLD-dependent phosphatidic acid microdomains are signaling platforms for podosome formation

The role of circadian rhythm in the regulation of cellular protein profiles in the brain

Pip5k1c Loss in Chondrocytes Causes Spontaneous Osteoarthritic Lesions in Aged Mice

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