title: Directed microtubule growth, +TIPs, and kinesin-2 are required for uniform microtubule polarity in dendrites.
abstract: BACKGROUND
  in many differentiated cells, microtubules are organized into polarized noncentrosomal arrays, yet few mechanisms that control these arrays have been identified. For example, mechanisms that maintain microtubule polarity in the face of constant remodeling by dynamic instability are not known. Drosophila neurons contain uniform-polarity minus-end-out microtubules in dendrites, which are often highly branched. Because undirected microtubule growth through dendrite branch points jeopardizes uniform microtubule polarity, we have used this system to understand how cells can maintain dynamic arrays of polarized microtubules.
  
  
  RESULTS
  we find that growing microtubules navigate dendrite branch points by turning the same way, toward the cell body, 98% of the time and that growing microtubules track along stable microtubules toward their plus ends. Using RNAi and genetic approaches, we show that kinesin-2, and the +TIPS EB1 and APC, are required for uniform dendrite microtubule polarity. Moreover, the protein-protein interactions and localization of Apc2-GFP and Apc-RFP to branch points suggests that these proteins work together at dendrite branches. The functional importance of this polarity mechanism is demonstrated by the failure of neurons with reduced kinesin-2 to regenerate an axon from a dendrite.
  
  
  CONCLUSIONS
  we conclude that microtubule growth is directed at dendrite branch points and that kinesin-2, APC, and EB1 are likely to play a role in this process. We propose that kinesin-2 is recruited to growing microtubules by +TIPS and that the motor protein steers growing microtubules at branch points. This represents a newly discovered mechanism for maintaining polarized arrays of microtubules.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Floyd J
authors.initials: FJ
authors.lastname: Mattie
authors.forename: Megan M
authors.initials: MM
authors.lastname: Stackpole
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Stone
authors.forename: Jessie R
authors.initials: JR
authors.lastname: Clippard
authors.forename: David A
authors.initials: DA
authors.lastname: Rudnick
authors.forename: Yijun
authors.initials: Y
authors.lastname: Qiu
authors.forename: Juan
authors.initials: J
authors.lastname: Tao
authors.forename: Dana L
authors.initials: DL
authors.lastname: Allender
authors.forename: Manpreet
authors.initials: M
authors.lastname: Parmar
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Rolls
mesh_terms: D000818:Animals; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C118001:APC protein, Drosophila; C467323:APC2 protein, Drosophila; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; C405804:EB1 microtubule binding proteins; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C525729:kinesin 2 protein, Drosophila; D016547:Kinesins