Essential Role of Type Iα Phosphatidylinositol 4-Phosphate 5-Kinase in Neurite Remodeling

Horck, Francis P.G. van; Lavazais, Emmanuelle; Eickholt, Britta J.; Moolenaar, Wouter H.; Divecha, Nullin

doi:10.1016/s0960-9822(01)00660-1

Cited by 66 publications

(52 citation statements)

References 24 publications

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“…We have shown recently that the RhoA effector, Rho-kinase, which mediates signals from RhoA to the actin cytoskeleton (36), is involved in RhoA-dependent regulation of PIP5K activity (37). In agreement, in intact CV1 cells (16) and platelets (38), PIP 2 formation is reduced by the Rhokinase inhibitor, Y27632, and in N1E-115 neuroblastoma cells, PIP5K functions as downstream effector of RhoA-and Rhokinase in neurite remodeling (39,40). Rho GTPases were also found to physically associate with type I PIP5K.…”

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confidence: 68%

Activation of Type I Phosphatidylinositol 4-Phosphate 5-Kinase Isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42

Weernink

Meletiadis

Hommeltenberg

et al. 2004

Journal of Biological Chemistry

158

139

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Type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) catalyzes the formation of the phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is implicated in many cellular processes. The Rho GTPases, RhoA and Rac1, have been shown previously to activate PIP5K and to bind PIP5K. Three type I PIP5K isoforms (I␣, I␤, and I␥) have been identified; however, it is unclear whether these isoforms are differentially or even sequentially regulated by Rho GTPases. Here we show that RhoA and Rac1, as well as Cdc42, but not the Ras-like GTPases, RalA and Rap1A, markedly stimulate PIP 2 synthesis by all three PIP5K isoforms expressed in human embryonic kidney 293 cells, both in vitro and in vivo. RhoA-stimulated PIP 2 synthesis by the PIP5K isoforms was mediated by the RhoA effector, Rho-kinase. Stimulation of PIP5K isoforms by Rac1 and Cdc42 was apparently independent of and additive with RhoA-and Rho-kinase, as shown by studies with C3 transferase and Rho-kinase mutants. RhoA, and to a lesser extent Rac1, but not Cdc42, interacted in a nucleotide-independent form with all three PIP5K isoforms. Binding of PIP5K isoforms to GTP-bound, but not GDP-bound, RhoA could be displaced by Rho-kinase, suggesting a direct and constitutive PIP5K-Rho GTPase binding, which, however, does not trigger PIP5K activation. In summary, our findings indicate that synthesis of PIP 2 by the three PIP5K isoforms is controlled by RhoA, acting via Rho-kinase, as well as Rac1 and Cdc42, implicating that regulation of PIP 2 synthesis has a central position in signaling by these three Rho GTPases.Synthesis and turnover of the membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP 2 ),

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mentioning

confidence: 68%

Activation of Type I Phosphatidylinositol 4-Phosphate 5-Kinase Isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42

Weernink

Meletiadis

Hommeltenberg

et al. 2004

Journal of Biological Chemistry

158

139

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“…In terms of their cellular functions, PIP5K1s are also involved in the regulation of actin reorganization and focal adhesion dynamics, which are critical in cell migration (51) and neurite outgrowth (52,53). Among all PIP5K1s, PIP5K1C is mainly expressed in brain and required for cardiovascular and neuronal development.…”

Section: Discussionmentioning

confidence: 99%

EZH2 Regulates Neuronal Differentiation of Mesenchymal Stem Cells through PIP5K1C-dependent Calcium Signaling

Chou

Chen

et al. 2011

Journal of Biological Chemistry

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Enhancer of zeste homolog 2 (EZH2) regulates stem cells renewal, maintenance, and differentiation into different cell lineages including neuron. Changes in intracellular Ca2؉ concentration play a critical role in the differentiation of neurons. However, whether EZH2 modulates intracellular Ca 2؉ signaling in regulating neuronal differentiation from human mesenchymal stem cells (hMSCs) still remains unclear. When hMSCs were treated with a Ca 2؉ chelator or a PLC inhibitor to block IP 3 -mediated Ca 2؉ signaling, neuronal differentiation was disrupted. EZH2 bound to the promoter region of PIP5K1C to suppress its transcription in proliferating hMSCs. Interestingly, knockdown of EZH2 enhanced the expression of PIP5K1C, which in turn increased the amount of PI(4,5)P 2 , a precursor of IP 3 , and resulted in increasing the intracellular Ca 2؉ level, suggesting that EZH2 negatively regulates intracellular Ca 2؉ through suppression of PIP5K1C. Knockdown of EZH2 also enhanced hMSCs differentiation into functional neuron both in vitro and in vivo. In contrast, knockdown of PIP5K1C significantly reduced PI(4,5)P 2 contents and intracellular Ca 2؉ release in EZH2-silenced cells and resulted in the disruption of neuronal differentiation from hMSCs. Here, we provide the first evidence to demonstrate that after induction to neuronal differentiation, decreased EZH2 activates the expression of PIP5K1C to evoke intracellular Ca 2؉ signaling, which leads hMSCs to differentiate into functional neuron lineage. Activation of intracellular Ca 2؉ signaling by repressing or knocking down EZH2 might be a potential strategy to promote neuronal differentiation from hMSCs for application to neurological dysfunction diseases. Human mesenchymal stem cells (hMSCs)4 derived from bone marrow are easily obtained (1), safely expanded in vitro and are not susceptible to malignant transformation; thus, hMSCs are suitable for therapeutic applications (2). hMSCs can be induced to differentiate into multiple lineages, including bone, fat, cartilage, as well as neuron in vitro (1,(3)(4)(5). Transplanted MSCs are able to differentiate into neuronal lineage and improve the functions of central nervous system (CNS) with ischemia (6), Parkinson disease (7), Alzheimer disease (8), spinal cord injury (9, 10), and other neurodegenerative disorders (11, 12) modeled in rodents. These findings demonstrate the potential of hMSCs for cell therapy in human CNS.Spontaneous and transient elevation in intracellular Ca 2ϩ concentration during an early period is required and critical for neuronal differentiation both in vitro and in embryonic neuron development (13). However, whether intracellular Ca 2ϩ signaling is required for neuronal differentiation from hMSCs remains unclear. The expression of transient receptor potential (TRP) proteins, TRPC1 and TRPC3, is elevated to activate store-operated calcium entry (SOCE) after differentiation of H19 -7 hippocampal neuronal cells (14). It is also known that inositol 1,4,5-trisphosphate (IP 3 ) stimulates a ligand-gated chann...

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“…Intriguingly, a previous report indicated that Sema3A-mediated neurite retraction requires instead the activity of another isoform of PIPK, © 2 0 0 6 C o p y r i g h t E u r e k a h / L a n d e s B i o s c i e n c e D o N o t D i s t r i b u t e called PIPK-Iα. 111 Although not localized to focal contacts, PIPK-Iα activity was shown to induce vinculin dissociation from the adhesive complexes and release substrate adhesion. 111 Therefore, the regulation of PIP2 levels at the cell surface seems to be an important mechanism to account for semaphorin-mediated control of cell-substrate adhesion and actin remodelling.…”

Section: Integrins and The Actin Cytoskeleton Are Major Targets Of Plmentioning

confidence: 99%

“…111 Although not localized to focal contacts, PIPK-Iα activity was shown to induce vinculin dissociation from the adhesive complexes and release substrate adhesion. 111 Therefore, the regulation of PIP2 levels at the cell surface seems to be an important mechanism to account for semaphorin-mediated control of cell-substrate adhesion and actin remodelling.…”

Section: Integrins and The Actin Cytoskeleton Are Major Targets Of Plmentioning

confidence: 99%

Semaphorin Signals in Cell Adhesion and Cell Migration: Functional Role and Molecular Mechanisms

Casazza¹,

Fazzari²,

Tamagnone

2007

Advances in Experimental Medicine and Biology

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C ell migration is pivotal in embryo development and in the adult. During development, a wide range of progenitor cells travel over long distances before undergoing terminal differentiation. Moreover, the morphogenesis of epithelial tissues and of the cardio-vascular system involves remodelling compact cell layers and the sprouting of new tubular branches. In the adult, cell migration is essential for the leucocytes involved in immune response. Furthermore, invasive and metastatic cancer cells have the distinctive ability to overcome normal tissue boundaries, travel in and out the blood vessels, and settle down in heterologous tissues. Cell migration normally follows strict guidance cues, either attractive, or inhibitory and repulsive. Semaphorins are a wide family of signals guiding cell migration during development and in the adult. Recent findings have established that semaphorin receptors, the plexins, govern cell migration by regulating integrin-based cell substrate adhesion and actin cytoskeleton dynamics, via specific monomeric GTPases. Plexins furthermore recruit tyrosine kinases in receptor complexes, which allows switching between multiple signalling pathways and functional outcomes. In this article, we will review the functional role of semaphorins in cell migration and the implicated molecular mechanisms controlling cell adhesion.

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Essential Role of Type Iα Phosphatidylinositol 4-Phosphate 5-Kinase in Neurite Remodeling

Cited by 66 publications

References 24 publications

Activation of Type I Phosphatidylinositol 4-Phosphate 5-Kinase Isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42

Activation of Type I Phosphatidylinositol 4-Phosphate 5-Kinase Isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42

EZH2 Regulates Neuronal Differentiation of Mesenchymal Stem Cells through PIP5K1C-dependent Calcium Signaling

Semaphorin Signals in Cell Adhesion and Cell Migration: Functional Role and Molecular Mechanisms

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