Role of the integrin-linked kinase (ILK) in determining neuronal polarity.
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.
Guo
Wei
W
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.
Jiang
Hui
H
Gray
Virginia
V
Dedhar
Shoukat
S
Rao
Yi
Y
D000818:Animals; D001369:Axons / Q000378:metabolism; D019521:Body Patterning; D004247:DNA / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000099200:Scaffold Protein ILK
D004247:DNA; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK; C000605506:GSK3B protein, human; C000605508:Gsk3b protein, rat