title: Kinesin-5, a mitotic microtubule-associated motor protein, modulates neuronal migration.
abstract: Kinesin-5 (also called Eg5 or kif11) is a homotetrameric motor protein that functions by modulating microtubule (MT)-MT interactions. In the case of mitosis, kinesin-5 slows the rate of separation of the half-spindles. In the case of the axon, kinesin-5 limits the frequency of transport of short MTs, and also limits the rate of axonal growth. Here we show that experimental inhibition of kinesin-5 in cultured migratory neurons results in a faster but more randomly moving neuron with a shorter leading process. As is the case with axons of stationary neurons, short MT transport frequency is notably enhanced in the leading process of the migratory neuron when kinesin-5 is inhibited. Conversely, overexpression of kinesin-5, both in culture and in developing cerebral cortex, causes migration to slow and even cease. Regions of anti-parallel MT organization behind the centrosome were shown to be especially rich in kinesin-5, implicating these regions as potential sites where kinesin-5 forces may be especially relevant. We posit that kinesin-5 acts as a "brake" on MT-MT interactions that modulates the advance of the entire MT apparatus. In so doing, kinesin-5 regulates the rate and directionality of neuronal migration and possibly the cessation of migration when the neuron reaches its destination.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Falnikar
authors.forename: Shubha
authors.initials: S
authors.lastname: Tole
authors.forename: Peter W
authors.initials: PW
authors.lastname: Baas
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton; D018274:Electroporation; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D008941:Spindle Apparatus / Q000378:metabolism; D013871:Thiones / Q000494:pharmacology
chemical_list: D011743:Pyrimidines; D034741:RNA, Small Interfering; D013871:Thiones; C400223:monastrol; D016547:Kinesins