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PMID:16369480

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Citation

Kholmanskikh, SS, Koeller, HB, Wynshaw-Boris, A, Gomez, T, Letourneau, PC and Ross, ME (2006) Calcium-dependent interaction of Lis1 with IQGAP1 and Cdc42 promotes neuronal motility. Nat. Neurosci. 9:50-7

Abstract

Lis1 gene defects impair neuronal migration, causing the severe human brain malformation lissencephaly. Although much is known about its interactions with microtubules, microtubule-binding proteins such as CLIP-170, and with the dynein motor complex, the response of Lis1 to neuronal motility signals has not been elucidated. Lis1 deficiency is associated with deregulation of the Rho-family GTPases Cdc42, Rac1 and RhoA, and ensuing actin cytoskeletal defects, but the link between Lis1 and Rho GTPases remains unclear. We report here that calcium influx enhances neuronal motility through Lis1-dependent regulation of Rho GTPases. Lis1 promotes Cdc42 activation through interaction with the calcium sensitive GTPase scaffolding protein IQGAP1, maintaining the perimembrane localization of IQGAP1 and CLIP170 and thereby tethering microtubule ends to the cortical actin cytoskeleton. Lis1 thus is a key component of neuronal motility signal transduction that regulates the cytoskeleton by complexing with IQGAP1, active Cdc42 and CLIP-170 upon calcium influx.

Links

PubMed Online version:10.1038/nn1619

Keywords

1-Alkyl-2-acetylglycerophosphocholine Esterase; Actins/metabolism; Aniline Compounds; Animals; Blotting, Western; Calcium/metabolism; Calcium/physiology; Cell Movement/physiology; Cells, Cultured; Fluorescent Dyes; Hippocampus/cytology; Hippocampus/metabolism; Immunohistochemistry; Immunoprecipitation; Mice; Mice, Knockout; Microscopy, Video; Microtubule-Associated Proteins/physiology; Neurons/physiology; Plasmids/genetics; Transfection; Xanthenes; cdc42 GTP-Binding Protein/physiology; ras GTPase-Activating Proteins/physiology; rho GTP-Binding Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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