title: Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization.
abstract: Kinesin-5 is a slow homotetrameric motor protein best known for its essential role in the mitotic spindle, where it limits the rate at which faster motors can move microtubules. In neurons, experimental suppression of kinesin-5 causes the axon to grow faster by increasing the mobility of microtubules in the axonal shaft and the invasion of microtubules into the growth cone. Does kinesin-5 act differently in dendrites, given that they have a population of minus end-distal microtubules not present in axons? Using rodent primary neurons in culture, we found that inhibition of kinesin-5 during various windows of time produces changes in dendritic morphology and microtubule organization. Specifically, dendrites became shorter and thinner and contained a greater proportion of minus end-distal microtubules, suggesting that kinesin-5 acting normally restrains the number of minus end-distal microtubules that are transported into dendrites. Additional data indicate that, in neurons, CDK5 is the kinase responsible for phosphorylating kinesin-5 at Thr-926, which is important for kinesin-5 to associate with microtubules. We also found that kinesin-5 associates preferentially with microtubules rich in tyrosinated tubulin. This is consistent with an observed accumulation of kinesin-5 on dendritic microtubules, as they are known to be less detyrosinated than axonal microtubules.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129.
authors.forename: Olga I
authors.initials: OI
authors.lastname: Kahn
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129.
authors.forename: Vandana
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Department of Biology and Institute for Cell Dynamics and Biotechnology (ICDB), Faculty of Sciences, Universidad de Chile, 7800024 Nunoa, Santiago, Chile.
authors.forename: Christian
authors.initials: C
authors.lastname: González-Billault
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129 pbaas@drexelmed.edu.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Baas
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D001692:Biological Transport; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D005260:Female; D020439:Growth Cones / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D008297:Male; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin; D051360:Cyclin-Dependent Kinase 5; D004398:Dyneins; D016547:Kinesins