Essential role of type I(alpha) phosphatidylinositol 4-phosphate 5-kinase in neurite remodeling
Essential role of type I(alpha) phosphatidylinositol 4-phosphate 5-kinase in neurite remodeling
Rapid neurite remodeling is fundamental to nervous system development and plasticity and is regulated by Rho family GTPases that signal f-actin reorganization in response to various receptor ligands. Neuronal N1E-115 cells show dramatic neurite retraction and cell rounding in response to serum factors such as lysophosphatidic acid (LPA), sphingosine-1 phosphate (S1P), and thrombin, due to activation of the RhoA-Rho kinase pathway. Type I phosphatidylinositol 4-phosphate 5-kinases (PIPkinase), which regulate cellular levels of PtdIns(4,5)P(2), have been suggested as targets of the RhoA-Rho kinase pathway able to modulate cytoskeletal dynamics. Here, we show that the introduction of Type Ialpha PIPkinase into N1E-115 cells leads to cell rounding and complete inhibition of neurite outgrowth, perhaps through the dissociation of vinculin and the destabilization of focal adhesions. This occurs independently of RhoA, Rho kinase, and the activation of actomyosin contraction. Strikingly, expression of kinase-dead PIPkinase promotes the outgrowth of neurites, which fail to retract in response to LPA, S1P, thrombin, or active RhoA. Moreover, neurite retraction in response to an endogenous neuronal guidance cue, Semaphorin3A, was also dependent on Type Ialpha PIPkinase. Our results suggest an essential role for a Type I PIPkinase during neurite retraction in response to a number of diverse stimuli.
Animals Cell Size/drug effects Cytoskeletal Proteins/metabolism Focal Adhesion Protein-Tyrosine Kinases Focal Adhesions/chemistry/metabolism Intracellular Signaling Peptides and Proteins Isoenzymes/antagonists & inhibitors/genetics/metabolism Lysophospholipids/pharmacology Mutation/genetics Myosin-Light-Chain Kinase/metabolism Neurites/drug effects/*enzymology/*metabolism Neurons/*cytology/drug effects/*enzymology Paxillin Phosphoproteins/metabolism Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/genetics/*metabolism Protein Serine-Threonine Kinases/metabolism Protein-Tyrosine Kinases/metabolism Tumor Cells, Cultured Vinculin/metabolism rho-Associated Kinases rhoA GTP-Binding Protein/metabolism
241-245
van Horck, F. P.
a258a4a7-9996-4bb0-8b9e-f8a42dc4c72a
Lavazais, E.
18c3e093-e969-4f4c-93ad-bdfa7504afa3
Eickholt, B. J.
01480969-5e50-48b1-9942-584bfef49e90
Moolenaar, W. H.
e97390b7-ebbe-485c-84e6-95fcab99182b
Divecha, N.
5c2ad0f8-4ce7-405f-8a15-2fc4ab96d787
5 February 2002
van Horck, F. P.
a258a4a7-9996-4bb0-8b9e-f8a42dc4c72a
Lavazais, E.
18c3e093-e969-4f4c-93ad-bdfa7504afa3
Eickholt, B. J.
01480969-5e50-48b1-9942-584bfef49e90
Moolenaar, W. H.
e97390b7-ebbe-485c-84e6-95fcab99182b
Divecha, N.
5c2ad0f8-4ce7-405f-8a15-2fc4ab96d787
van Horck, F. P., Lavazais, E., Eickholt, B. J., Moolenaar, W. H. and Divecha, N.
(2002)
Essential role of type I(alpha) phosphatidylinositol 4-phosphate 5-kinase in neurite remodeling.
Current Biology, 12 (3), .
(doi:10.1016/s0960-9822(01)00660-1).
Abstract
Rapid neurite remodeling is fundamental to nervous system development and plasticity and is regulated by Rho family GTPases that signal f-actin reorganization in response to various receptor ligands. Neuronal N1E-115 cells show dramatic neurite retraction and cell rounding in response to serum factors such as lysophosphatidic acid (LPA), sphingosine-1 phosphate (S1P), and thrombin, due to activation of the RhoA-Rho kinase pathway. Type I phosphatidylinositol 4-phosphate 5-kinases (PIPkinase), which regulate cellular levels of PtdIns(4,5)P(2), have been suggested as targets of the RhoA-Rho kinase pathway able to modulate cytoskeletal dynamics. Here, we show that the introduction of Type Ialpha PIPkinase into N1E-115 cells leads to cell rounding and complete inhibition of neurite outgrowth, perhaps through the dissociation of vinculin and the destabilization of focal adhesions. This occurs independently of RhoA, Rho kinase, and the activation of actomyosin contraction. Strikingly, expression of kinase-dead PIPkinase promotes the outgrowth of neurites, which fail to retract in response to LPA, S1P, thrombin, or active RhoA. Moreover, neurite retraction in response to an endogenous neuronal guidance cue, Semaphorin3A, was also dependent on Type Ialpha PIPkinase. Our results suggest an essential role for a Type I PIPkinase during neurite retraction in response to a number of diverse stimuli.
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More information
Published date: 5 February 2002
Additional Information:
van Horck, Francis P G Lavazais, Emmanuelle Eickholt, Britta J Moolenaar, Wouter H Divecha, Nullin eng Research Support, Non-U.S. Gov't England 2002/02/13 Curr Biol. 2002 Feb 5;12(3):241-5. doi: 10.1016/s0960-9822(01)00660-1.
Keywords:
Animals Cell Size/drug effects Cytoskeletal Proteins/metabolism Focal Adhesion Protein-Tyrosine Kinases Focal Adhesions/chemistry/metabolism Intracellular Signaling Peptides and Proteins Isoenzymes/antagonists & inhibitors/genetics/metabolism Lysophospholipids/pharmacology Mutation/genetics Myosin-Light-Chain Kinase/metabolism Neurites/drug effects/*enzymology/*metabolism Neurons/*cytology/drug effects/*enzymology Paxillin Phosphoproteins/metabolism Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/genetics/*metabolism Protein Serine-Threonine Kinases/metabolism Protein-Tyrosine Kinases/metabolism Tumor Cells, Cultured Vinculin/metabolism rho-Associated Kinases rhoA GTP-Binding Protein/metabolism
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Local EPrints ID: 479753
URI: http://eprints.soton.ac.uk/id/eprint/479753
ISSN: 0960-9822
PURE UUID: 7af1f3d8-df35-4770-8dea-6f12e2b6e2b2
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Date deposited: 26 Jul 2023 16:56
Last modified: 17 Mar 2024 03:00
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Author:
F. P. van Horck
Author:
E. Lavazais
Author:
B. J. Eickholt
Author:
W. H. Moolenaar
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