Article ID Journal Published Year Pages File Type
2175218 Developmental Biology 2007 12 Pages PDF
Abstract

The establishment of axon–dendrite polarity in mammalian neurons has recently been shown to involve the kinases Akt and GSK-3β. 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-3β. Manipulations of multiple intracellular components indicate that ILK is functionally upstream of Akt and GSK-3β 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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