title: The microtubule lattice and plus-end association of Drosophila Mini spindles is spatially regulated to fine-tune microtubule dynamics.
abstract: Individual microtubules (MTs) exhibit dynamic instability, a behavior in which they cycle between phases of growth and shrinkage while the total amount of MT polymer remains constant. Dynamic instability is promoted by the conserved XMAP215/Dis1 family of microtubule-associated proteins (MAPs). In this study, we conducted an in vivo structure-function analysis of the Drosophila homologue Mini spindles (Msps). Msps exhibits EB1-dependent and spatially regulated MT localization, targeting to microtubule plus ends in the cell interior and decorating the lattice of growing and shrinking microtubules in the cell periphery. RNA interference rescue experiments revealed that the NH(2)-terminal four TOG domains of Msps function as paired units and were sufficient to promote microtubule dynamics and EB1 comet formation. We also identified TOG5 and novel inter-TOG linker motifs that are required for targeting Msps to the microtubule lattice. These novel microtubule contact sites are necessary for the interplay between the conserved TOG domains and inter-TOG MT binding that underlies the ability of Msps to promote MT dynamic instability.
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Currie
authors.forename: Shannon
authors.initials: S
authors.lastname: Stewman
authors.forename: Gregory
authors.initials: G
authors.lastname: Schimizzi
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Slep
authors.forename: Ao
authors.initials: A
authors.lastname: Ma
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Rogers
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C405804:EB1 microtubule binding proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C121511:msps protein, Drosophila