Role of the integrin-linked kinase (ILK) in determining neuronal polarity |
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Authors: | Guo Wei Jiang Hui Gray Virginia Dedhar Shoukat Rao Yi |
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Institution: | Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. |
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Abstract: | The establishment of axon-dendrite polarity in mammalian neurons has recently been shown to involve the kinases Akt and GSK-3beta. Here we report the function of the integrin-linked kinase (ILK) in neuronal polarization. ILK distribution is differential: with more of it present in the axonal tips than that in the dendritic tips of a polarized neuron. Inactivation of ILK by chemical inhibitors, a kinase-inactive mutant or siRNAs inhibited axon formation, whereas a kinase hyperactive ILK mutant induced the formation of multiple axons. Biochemical studies indicate that ILK is upstream of Akt and GSK-3beta. Manipulations of multiple intracellular components indicate that ILK is functionally upstream of Akt and GSK-3beta but downstream of PI3K in neuronal polarity. These results reveal a key role of ILK in the formation of neuronal polarity and suggest a signaling pathway important for neuronal polarity. |
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Keywords: | Integrin-linked kinase Neuronal polarity Glycogen synthase kinase-3β Akt PI3K Axon determination |
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