Vibrator and PI4KIIIα govern neuroblast polarity by anchoring non-muscle myosin II

Koe, Chwee Tat; Tan, Yan; Lönnfors, Max; Hur, Seong Kwon; Low, Christine Siok Lan; Zhang, Yingjie; Kanchanawong, Pakorn; Bankaitis, Vytas A.; Wang, Hongyan

doi:10.7554/elife.33555

Cited by 22 publications

(24 citation statements)

References 82 publications

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“…Cells (5 × 10 4 per well) were seeded into 8-well chamber slides (Lab-Tek, Cat# 154941). The plasmids used were control Myc [53], control Flag [53], Flag-Wts, and Myc-Mahj, Myc-DDB1, and Myc-Cul4 with 50 ng of each plasmid per sample. Forty-eight hours after transfection, S2 cells were rinsed once with cold PBS, fixed with 4% formaldehyde in PBS for 15 min, and blocked in 5% BSA in PBST (0.1% Triton-X100) for 45 min.…”

Section: Methodsmentioning

confidence: 99%

CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation

Tan

Koe

et al. 2019

PLoS Biol

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The ability of neural stem cells (NSCs) to transit between quiescence and proliferation is crucial for brain development and homeostasis. Drosophila Hippo pathway maintains NSC quiescence, but its regulation during brain development remains unknown. Here, we show that CRL4 Mahj , an evolutionarily conserved E3 ubiquitin ligase, is essential for NSC reactivation (exit from quiescence). We demonstrate that damaged DNA-binding protein 1 (DDB1) and Cullin4, two core components of Cullin4-RING ligase (CRL4), are intrinsically required for NSC reactivation. We have identified a substrate receptor of CRL4, Mahjong (Mahj), which is necessary and sufficient for NSC reactivation. Moreover, we show that CRL4 Mahj forms a protein complex with Warts (Wts/large tumor suppressor [Lats]), a kinase of the Hippo signaling pathway, and Mahj promotes the ubiquitination of Wts. Our genetic analyses further support the conclusion that CRL4 Mahj triggers NSC reactivation by inhibition of Wts. Given that Cullin4B mutations cause mental retardation and cerebral malformation, similar regulatory mechanisms may be applied to the human brain.

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Section: Methodsmentioning

confidence: 99%

CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation

Tan

Koe

et al. 2019

PLoS Biol

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“…In Drosophila, larval neuroblasts act as NSCs to generate all of the neurons and glia in adult flies. Recent data have shown that the PI regulating enzymes Vibrator and PI4 kinase IIIa (PI4KIIIa) are required for the asymmetric distribution of cell fate determinants in neuroblasts (Koe et al, 2018). Mutations that affect the PI binding and PI lipid transfer activities of Vibrator induce defects in neuroblast asymmetric division, leading to either the formation of ectopic neuroblasts or their loss through differentiation into neurons.…”

Section: Lipids and Asymmetric Cell Divisionmentioning

confidence: 99%

Lipid Mediated Regulation of Adult Stem Cell Behavior

Clémot

Demarco

Jones

2020

Front. Cell Dev. Biol.

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Adult stem cells constitute an important reservoir of self-renewing progenitor cells and are crucial for maintaining tissue and organ homeostasis. The capacity of stem cells to self-renew or differentiate can be attributed to distinct metabolic states, and it is now becoming apparent that metabolism plays instructive roles in stem cell fate decisions. Lipids are an extremely vast class of biomolecules, with essential roles in energy homeostasis, membrane structure and signaling. Imbalances in lipid homeostasis can result in lipotoxicity, cell death and diseases, such as cardiovascular disease, insulin resistance and diabetes, autoimmune disorders and cancer. Therefore, understanding how lipid metabolism affects stem cell behavior offers promising perspectives for the development of novel approaches to control stem cell behavior either in vitro or in patients, by modulating lipid metabolic pathways pharmacologically or through diet. In this review, we will first address how recent progress in lipidomics has created new opportunities to uncover stem-cell specific lipidomes. In addition, genetic and/or pharmacological modulation of lipid metabolism have shown the involvement of specific pathways, such as fatty acid oxidation (FAO), in regulating adult stem cell behavior. We will describe and compare findings obtained in multiple stem cell models in order to provide an assessment on whether unique lipid metabolic pathways may commonly regulate stem cell behavior. We will then review characterized and potential molecular mechanisms through which lipids can affect stem cell-specific properties, including self-renewal, differentiation potential or interaction with the niche. Finally, we aim to summarize the current knowledge of how alterations in lipid homeostasis that occur as a consequence of changes in diet, aging or disease can impact stem cells and, consequently, tissue homeostasis and repair.

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“…It seems so. The sole Drosophila class I PITP [vibrator (Vib)] was identified in a genetic screen for mutants with dysregulated neuroblast homeostasis and self-renewal (205). Indeed, Vib regulates asymmetric division of neuroblasts (i.e., fly orthologs of neural stem cells) by anchoring the nonmuscle myosin II regulatory light chain Spaghetti-squash (Sph) to the cell cortex during cell division, thereby promoting the asymmetric partitioning of cellular components involved in cell fate determination as well as cytokinesis (206,207).…”

Section: In Vivo Class I Pitps and Embryonic Development Of The Mammamentioning

confidence: 99%

“…Indeed, Vib regulates asymmetric division of neuroblasts (i.e., fly orthologs of neural stem cells) by anchoring the nonmuscle myosin II regulatory light chain Spaghetti-squash (Sph) to the cell cortex during cell division, thereby promoting the asymmetric partitioning of cellular components involved in cell fate determination as well as cytokinesis (206,207). Vib is inferred to cooperate with PI4KIIIa to maintain a PtdIns4P pool on the neuroblast cell cortex for Sph recruitment (205).…”

Section: In Vivo Class I Pitps and Embryonic Development Of The Mammamentioning

confidence: 99%

The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes

Grabon

Bankaitis

McDermott

2019

Journal of Lipid Research

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P 3 ]. Yeasts (Saccharomyces) synthesize all of these except PtdIns(3,4)P 2 and PtdIns(3,4,5)P 3. This cohort of molecules is produced by a series of reversible phosphorylation and dephosphorylation reactions catalyzed by phosphoinositide kinases (PIKs) and phosphatases, respectively, that target the inositol headgroup at positions C3, C4, and C5 (1, 2). These chemically distinct lipids, although small in number, control an impressively large set of intracellular activities. How is such diversification of biological function achieved? Current views for how PtdIns and phosphoinositide signaling are diversified focus on regulatory mechanisms that include: the regulation and localization of the enzymes that produce, degrade, or sequester phosphoinositides; the identities of the effector proteins that recognize these Abstract Phosphoinositides are key regulators of a large number of diverse cellular processes that include membrane trafficking, plasma membrane receptor signaling, cell proliferation, and transcription. How a small number of chemically distinct phosphoinositide signals are functionally amplified to exert specific control over such a diverse set of biological outcomes remains incompletely understood. To this end, a novel mechanism is now taking shape, and it involves phosphatidylinositol (PtdIns) transfer proteins (PITPs). The concept that PITPs exert instructive regulation of PtdIns 4-OH kinase activities and thereby channel phosphoinositide production to specific biological outcomes, identifies PITPs as central factors in the diversification of phosphoinositide signaling. There are two evolutionarily distinct families of PITPs: the Sec14-like and the StAR-related lipid transfer domain (START)-like families. Of these two families, the START-like PITPs are the least understood. Herein, we review recent insights into the biochemical, cellular, and physiological function of both PITP families with greater emphasis on the START-like PITPs, and we discuss the underlying mechanisms through which these proteins regulate phosphoinositide signaling and how these actions translate to human health and disease.-Grabon, A., V. A. Bankaitis, and M. I. McDermott. The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes.

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Vibrator and PI4KIIIα govern neuroblast polarity by anchoring non-muscle myosin II

Cited by 22 publications

References 82 publications

CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation

CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation

Lipid Mediated Regulation of Adult Stem Cell Behavior

The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes

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