Phosphatidylinositol 4-phosphate 5-kinase is essential for ROCK-mediated neurite remodeling.
Phosphatidylinositol 4-phosphate 5-kinase (PIP-5kin) regulates actin cytoskeletal reorganization through its product phosphatidylinositol 4,5-bisphosphate. In the present study we demonstrate that PIP-5kin is essential for neurite remodeling, which is regulated by actin cytoskeletal reorganization in neuroblastoma N1E-115 cells. Overexpression of wild-type mouse PIP-5kin-alpha inhibits the neurite formation that is normally stimulated by serum depletion, whereas a lipid kinase-defective mutant of PIP-5kin-alpha, D266A, triggers neurite extension even in the presence of serum and blocks lysophosphatidic acid-induced neurite retraction. These results phenocopy those previously reported for the small GTPase RhoA and its effector p160 Rho-associated coiled coil-forming protein kinase (ROCK). However, the ROCK-specific inhibitor Y-27632 failed to block the inhibition by PIP-5kin-alpha of neurite extension, whereas D266A did block the neurite retraction induced by overexpression of ROCK. These results, taken together, suggest that PIP-5kin-alpha functions as a downstream effector for RhoA/ROCK to couple lysophosphatidic acid signaling to neurite retraction presumably through its product phosphatidylinositol 4,5-bisphosphate.
Yamazaki
Masakazu
M
Department of Pharmacology, the Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Miyazaki
Hideyuki
H
Watanabe
Hiroshi
H
Sasaki
Takehiko
T
Maehama
Tomohiko
T
Frohman
Michael A
MA
Kanaho
Yasunori
Y
D000577:Amides / Q000494:pharmacology; D000818:Animals; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009218:Myosins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D054460:rho-Associated Kinases
D000577:Amides; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008246:Lysophospholipids; D011725:Pyridines; D011993:Recombinant Fusion Proteins; C108830:Y 27632; D049452:Green Fluorescent Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009218:Myosins