Role of the integrin-linked kinase (ILK) in detennining neuronal polarity

The establishment of axon-dendrite polarity in mammalian neurons has recently been shown to involve the kinases Akt and GSK-3 beta. 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-3 beta. Manipulations of multiple intracellular components indicate that ILK is functionally upstream of Akt and GSK-3 beta 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. (C) 2007 Elsevier Inc. All rights reserved.