The impact of phosphoinositide 5-phosphatases on phosphoinositides in cell function and human disease

Ramos, António Manuel Pinho; Ghosh, Somadri; Erneux, Christophé

doi:10.1194/jlr.r087908

Cited by 35 publications

(42 citation statements)

References 110 publications

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“…It is anchored at the plasma membrane (De Smedt et al, 1997). The other members can use either PI(4,5)P2, PI(3,4,5)P3 or PI(3,5)P2 as substrate with different specificities (Ramos et al, 2019b). For example, SHIP1/2 are mainly recognized as PI(3,4,5)P3 5-phosphatases with the ability of producing PI(3,4)P2 in intact cells as reaction product (Backers et al, 2003;Balla, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Phosphoinositide (PI) 5-phosphatase i.e. OCRL, INPP5B, SHIP1/2, Synaptojanin 1/2, INPP5E, INPP5J, SKIP (INPP5K) are enzymes that dephosphorylate the 5-phosphate position of PIs (Dickson and Hille, 2019;Ramos et al, 2019b). They participate in both the cellular, spatial and temporal presence of PIs and derived functions in mitosis, apoptosis, migration or invasion … PI 5-phosphatases are very much involved in various human genetic diseases (Staiano et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…SKIP could use both PI(3,4,5)P3 and PI(4,5)P2 as substrate (Ijuin et al, 2000). Those lipids show multiple signaling properties in cell survival and membrane dynamics (Dickson and Hille, 2019;Ramos et al, 2019b). Moreover, SKIP has been reported to localize in ruffles, as SHIP2 (Hasegawa et al, 2011) but also at the surface of the endoplasmic reticulum (ER) which is unique amongst the various PI 5-phosphatases (Dong et al, 2018;Gurung et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update

Ramos

Ghosh

Suhel

et al. 2020

Advances in Biological Regulation

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Phosphoinositides (PIs) are phosphorylated derivatives of phosphatidylinositol. They act as signaling molecules linked to essential cellular mechanisms in eukaryotic cells, such as cytoskeleton organization, mitosis, polarity, migration or invasion. PIs are phosphorylated and dephosphorylated by a large number of PI kinases and PI phosphatases acting at the 5-, 4-and 3position of the inositol ring. PI 5-phosphatases i.e. OCRL, INPP5B, SHIP1/2, Synaptojanin 1/2, INPP5E, INPP5J, SKIP (INPP5K) are enzymes that dephosphorylate the 5-phosphate position of PIs. Several human genetic diseases such as the Lowe syndrome, some congenital muscular dystrophy and opsismodysplasia are due to mutations in PI phosphatases, resulting in loss-offunction. The PI phosphatases are also up or down regulated in several human cancers such as glioblastoma or breast cancer. Their cellular localization, that is dynamic and varies in response to stimuli, is an important issue to understand function. This is the case for two members of the PI 5-phosphatase SKIP and SHIP2. Both enzymes are in ruffles, plasma membranes, the endoplasmic reticulum, a situation that is unique for SKIP, and the nucleus. Following localization, PI 5phosphatases act on specific cellular pools of PIs, which in turn interact with target proteins. Nuclear PIs have emerged as regulators of genome functions in different area of cell signaling. They often localize to nuclear speckles, as do several PI metabolizing kinases and phosphatases. We asked whether SKIP and SHIP2 could have an impact on nuclear PI(4,5)P2. In two glioblastoma cell models, lowering SKIP expression had an impact on nuclear PI(4,5)P2. In a model of SHIP2 deletion in MCF-7 cells, no change in nuclear PI(4,5)P2 was observed. Finally, we present evidence of an anti-tumoral role of SKIP in vivo, in xenografts using as model U87shSKIP cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update

Ramos

Ghosh

Suhel

et al. 2020

Advances in Biological Regulation

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“…However, in unstimulated cells, only minor amounts of PtdIns(3,4,5)P 3 are found within the cytosolic leaflet of the PM and even at the maximal levels achieved upon receptor‐mediated activation of class I PI3Ks, PtdIns(3,4,5)P 3 only represent 2‐5% of the PtdIns(4,5)P 2 levels within the PM . As a result, the balance of PtdIns(3,4,5)P 3 production within the PM is unlikely to directly alter the bulk availability of PtdIns(4,5)P 2 , but dephosphorylation of PtdIns(3,4,5)P 3 by five‐position phosphatases has been shown to generate PtdIns(3,4)P 2 within the PM . Despite much debate about the relative importance of the kinase‐ and phosphatase‐dependent metabolic pathways for producing PtdIns(3,4)P 2, there is compelling evidence for the local production of PtdIns(3,4)P 2 by Class II PI3Ks within the PM and early endocytic structures .…”

Section: Production Of Polyphosphoinositide Species Within the Pmmentioning

confidence: 99%

Integrated regulation of the phosphatidylinositol cycle and phosphoinositide‐driven lipid transport at ER‐PM contact sites

Pemberton

Kim

Balla

2019

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Among the structural phospholipids that form the bulk of eukaryotic cell membranes, phosphatidylinositol (PtdIns) is unique in that it also serves as the common precursor for low-abundance regulatory lipids, collectively referred to as polyphosphoinositides (PPIn). The metabolic turnover of PPIn species has received immense attention because of the essential functions of these lipids as universal regulators of membrane biology and their dysregulation in numerous human pathologies. The diverse functions of PPIn lipids occur, in part, by orchestrating the spatial organization and conformational dynamics of peripheral or integral membrane proteins within defined subcellular compartments. The emerging role of stable contact sites between adjacent membranes as specialized platforms for the coordinate control of ion exchange, cytoskeletal dynamics, and lipid transport has also revealed important new roles for PPIn species. In this review, we highlight the importance of membrane contact sites formed between the endoplasmic reticulum (ER) and plasma membrane (PM) for the integrated regulation of PPIn metabolism within the PM. Special emphasis will be placed on non-vesicular lipid transport during control of the PtdIns biosynthetic cycle as well as toward balancing the turnover of the signaling PPIn species that define PM identity. K E Y W O R D SCRAL-TRIO, intracellular transport, lipid transfer protein, membrane contact sites, nonvesicular lipid transport, oxysterol-binding protein-related protein, phosphatidylinositol, phosphatidylinositol transfer protein, phosphoinositides, phospholipid metabolism, signal transduction, StARkin, TUbular LIPid-binding

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“…These members share an inositol 5-phosphatase domain with a set of conserved amino acids and a general comparable structural organization. Except for one member, INPP5A, they all catalyze the dephosphorylation of PtdIns(4,5)P2 and/or PtdIns(3,4,5)P3 at the 5-position, generating PtdIns(4)P and/or PtdIns(3,4)P2, respectively (Ramos et al, 2019a). Interestingly, 5phosphatase isoenzymes have been individually implicated in human diseases, such as ciliopathies (INPP5E), the oculo-cerebrorenal syndrome of Lowe (INPP5F) or opsismodysplasia, a rare congenital skeletal dysplasia (INPPL1) (Ramos et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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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The impact of phosphoinositide 5-phosphatases on phosphoinositides in cell function and human disease

Cited by 35 publications

References 110 publications

Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update

Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update

Integrated regulation of the phosphatidylinositol cycle and phosphoinositide‐driven lipid transport at ER‐PM contact sites

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

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