IPIP27 Coordinates PtdIns(4,5)P2 Homeostasis for Successful Cytokinesis

Carim, Sabrya; Kadhi, Khaled Ben El; Yan, Guanhua; Sweeney, Sean T.; Hickson, Gilles R.X.; Carréno, Sébastien; Lowe, Martin

doi:10.1016/j.cub.2019.01.043

Cited by 14 publications

(11 citation statements)

References 61 publications

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“…Although OCRL is not a recognised oncoprotein it has been implicated in processes relevant to cancer. OCRL is required for the successful completion of cytokinesis (276), a non-Golgi process that is often impaired during tumour growth (276,277). Interestingly the PI4P phosphatase Sac1 (201) and PI4KIIIβ orthologues (101,131,132,204,(278)(279)(280)(281) also possess mitotic functions.…”

Section: Ocrl As a Potential Source Of Pi4p And Suppressor Of Pi(45)mentioning

confidence: 99%

The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer)

Waugh

2019

Biochemical Journal

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Phosphatidylinositol 4-phosphate (PI4P) is a membrane glycerophospholipid and a major regulator of the characteristic appearance of the Golgi complex as well as its vesicular trafficking, signalling and metabolic functions. Phosphatidylinositol 4-kinases, and in particular the PI4KIIIβ isoform, act in concert with PI4P to recruit macromolecular complexes to initiate the biogenesis of trafficking vesicles for several Golgi exit routes. Dysregulation of Golgi PI4P metabolism and the PI4P protein interactome features in many cancers and is often associated with tumour progression and a poor prognosis. Increased expression of PI4P-binding proteins, such as GOLPH3 or PITPNC1, induces a malignant secretory phenotype and the release of proteins that can remodel the extracellular matrix, promote angiogenesis and enhance cell motility. Aberrant Golgi PI4P metabolism can also result in the impaired post-translational modification of proteins required for focal adhesion formation and cell–matrix interactions, thereby potentiating the development of aggressive metastatic and invasive tumours. Altered expression of the Golgi-targeted PI 4-kinases, PI4KIIIβ, PI4KIIα and PI4KIIβ, or the PI4P phosphate Sac1, can also modulate oncogenic signalling through effects on TGN-endosomal trafficking. A Golgi trafficking role for a PIP 5-kinase has been recently described, which indicates that PI4P is not the only functionally important phosphoinositide at this subcellular location. This review charts new developments in our understanding of phosphatidylinositol 4-kinase function at the Golgi and how PI4P-dependent trafficking can be deregulated in malignant disease.

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Section: Ocrl As a Potential Source Of Pi4p And Suppressor Of Pi(45)mentioning

confidence: 99%

The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer)

Waugh

2019

Biochemical Journal

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“…We and others have previously reported that depletion of OCRL1 or depletion of dOCRL, its Drosophila melanogaster orthologue, causes several characteristic phenotypes: abnormal accumulation of PtdIns(4,5)P 2 on endosomes, disorganization of the endocytic compartments, and cytokinetic defects (Ungewickell et al, 2004; Choudhury et al, 2005; Erdmann et al, 2007; Ben El Kadhi et al, 2011, 2012; Dambournet et al, 2011; Vicinanza et al, 2011; Nández et al, 2014; Cauvin et al, 2016; De Leo et al, 2016; Del Signore et al, 2017; Carim et al, 2019). In control dividing cells, PtdIns(4,5)P 2 concentrates at the cortical equator (Emoto et al, 2005; Field et al, 2005; Roubinet et al, 2011) and recruits the cytokinetic machinery that allows subsequent cytokinesis (Ben El Kadhi et al, 2011; Liu et al, 2012; Cauvin and Echard, 2015).…”

Section: Introductionmentioning

confidence: 97%

PTEN reduces endosomal PtdIns(4,5)P2 in a phosphatase-independent manner via a PLC pathway

Mondin

Kadhi

Cauvin

et al. 2019

Journal of Cell Biology

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The tumor suppressor PTEN dephosphorylates PtdIns(3,4,5)P3 into PtdIns(4,5)P2. Here, we make the unexpected discovery that in Drosophila melanogaster PTEN reduces PtdIns(4,5)P2 levels on endosomes, independently of its phosphatase activity. This new PTEN function requires the enzymatic action of dPLCXD, an atypical phospholipase C. Importantly, we discovered that this novel PTEN/dPLCXD pathway can compensate for depletion of dOCRL, a PtdIns(4,5)P2 phosphatase. Mutation of OCRL1, the human orthologue of dOCRL, causes oculocerebrorenal Lowe syndrome, a rare multisystemic genetic disease. Both OCRL1 and dOCRL loss have been shown to promote accumulation of PtdIns(4,5)P2 on endosomes and cytokinesis defects. Here, we show that PTEN or dPLCXD overexpression prevents these defects. In addition, we found that chemical activation of this pathway restores normal cytokinesis in human Lowe syndrome cells and rescues OCRL phenotypes in a zebrafish Lowe syndrome model. Our findings identify a novel PTEN/dPLCXD pathway that controls PtdIns(4,5)P2 levels on endosomes. They also point to a potential new strategy for the treatment of Lowe syndrome.

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“…This is achieved, in part, through the coordinated actions of various PI(4,5)P 2 phosphatases. For example, the PI(4,5)P 2 5-phosphatase, OCRL1, facilitates the removal of PI(4,5)P 2 from endosomes by acting at multiple sites, including in endosomes and during late stages of clathrin-mediated endocytosis 20 – 27 . In addition, synaptojanin, another major PI(4,5)P 2 phosphatase with 4- and 5-phosphatase activities, removes PI(4,5)P 2 from clathrin-coated membranes and facilitates clathrin disassembly during clathrin-mediated endocytosis 28 – 32 .…”

Section: Introductionmentioning

confidence: 99%

PDZD-8 and TEX-2 regulate endosomal PI(4,5)P2 homeostasis via lipid transport to promote embryogenesis in C. elegans

et al. 2021

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Different types of cellular membranes have unique lipid compositions that are important for their functional identity. PI(4,5)P2 is enriched in the plasma membrane where it contributes to local activation of key cellular events, including actomyosin contraction and cytokinesis. However, how cells prevent PI(4,5)P2 from accumulating in intracellular membrane compartments, despite constant intermixing and exchange of lipid membranes, is poorly understood. Using the C. elegans early embryo as our model system, we show that the evolutionarily conserved lipid transfer proteins, PDZD-8 and TEX-2, act together with the PI(4,5)P2 phosphatases, OCRL-1 and UNC-26/synaptojanin, to prevent the build-up of PI(4,5)P2 on endosomal membranes. In the absence of these four proteins, large amounts of PI(4,5)P2 accumulate on endosomes, leading to embryonic lethality due to ectopic recruitment of proteins involved in actomyosin contractility. PDZD-8 localizes to the endoplasmic reticulum and regulates endosomal PI(4,5)P2 levels via its lipid harboring SMP domain. Accumulation of PI(4,5)P2 on endosomes is accompanied by impairment of their degradative capacity. Thus, cells use multiple redundant systems to maintain endosomal PI(4,5)P2 homeostasis.

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IPIP27 Coordinates PtdIns(4,5)P2 Homeostasis for Successful Cytokinesis

Cited by 14 publications

References 61 publications

The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer)

The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer)

PTEN reduces endosomal PtdIns(4,5)P2 in a phosphatase-independent manner via a PLC pathway

PDZD-8 and TEX-2 regulate endosomal PI(4,5)P2 homeostasis via lipid transport to promote embryogenesis in C. elegans

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