title: TPX2 regulates neuronal morphology through kinesin-5 interaction.
abstract: TPX2 (targeting protein for Xklp2) is a multifunctional mitotic spindle assembly factor that in mammalian cells localizes and regulates mitotic motor protein kinesin-5 (also called Eg5 or kif11). We previously showed that upon depletion or inhibition of kinesin-5 in cultured neurons, microtubule movements increase, resulting in faster growing axons and thinner dendrites. Here, we show that depletion of TPX2 from cultured neurons speeds their rate of process outgrowth, similarly to kinesin-5 inhibition. The phenotype is rescued by TPX2 re-expression, but not if TPX2's kinesin-5-interacting domain is deleted. These results, together with studies showing a spike in TPX2 expression during dendritic differentiation, suggest that the levels and distribution of TPX2 are likely to be determinants of when and where kinesin-5 acts in neurons.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Olga I
authors.initials: OI
authors.lastname: Kahn
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Ngoc
authors.initials: N
authors.lastname: Ha
authors.affiliation: National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, Florida.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Baird
authors.affiliation: National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, Florida.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Davidson
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Baas
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; C470243:KIF11 protein, human; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C122167:TPX2 protein, human; D016547:Kinesins
keywords: Eg5; TPX2; kif11; microtubule; molecular motor; neuron