Roles of lipid rafts in integrin-dependent adhesion and gp130 signalling pathway in mouse embryonic neural precursor cells.
Neuronal and glial cells organizing the central nervous system are generated from common neural precursor cells present in the neuroepithelium during development. We tried to clarify functions of a cell surface microdomain, lipid raft, in neuroepithelial cells (NECs). NECs are suggested to adhere to fibronectin substratum dependently on integrin molecules. We found that beta1 integrin, a component of fibronectin receptors, was distributed in lipid rafts. Methyl-beta-cyclodextrin (MBCD), an inhibitor of lipid raft formation, inhibited the integrin-fibronectin interaction-dependent adhesion of NECs. However, inhibition of synthesis of glycosphingolipids (GSL), components of lipid rafts, did not affect NEC adhesion. Leukaemia inhibitory factor (LIF), an interleukin 6 type cytokine, induces astrocyte differentiation of NECs via activation of a transcription factor STAT3. We detected gp130, JAK1 and Ras but not STAT3 and ERK2 molecules in lipid rafts of NECs. Disruption of lipid rafts by MBCD inhibited LIF-induced ERK activation but not STAT3 activation. It is thus suggested that LIF-downstream molecules have differential lipid raft-dependency in terms of activation upon LIF-stimulation. In this study, we found functions of lipid rafts in cell adhesion and signal transduction in NECs. This is the first report that characterized functions of lipid rafts in embryonic neural precursor cells.
The 21st Century COE program Cell Fate Regulation Research and Education Unit, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan.
Makoto
M
Yanagisawa
Kazuo
K
Nakamura
Tetsuya
T
Taga
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003505:Cyclodextrins / Q000494:pharmacology; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology*; D005353:Fibronectins / Q000502:physiology; D006028:Glycosphingolipids / Q000502:physiology; D019012:Integrin beta1 / Q000032:analysis; D016023:Integrins / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D047392:beta-Cyclodextrins
D015703:Antigens, CD; D003505:Cyclodextrins; D004268:DNA-Binding Proteins; D005353:Fibronectins; D006028:Glycosphingolipids; C494200:Il6st protein, mouse; D019012:Integrin beta1; D016023:Integrins; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D050822:Cytokine Receptor gp130