title: Drosophila CLIP-190 and mammalian CLIP-170 display reduced microtubule plus end association in the nervous system.
abstract: Axons act like cables, electrically wiring the nervous system. Polar bundles of microtubules (MTs) form their backbones and drive their growth. Plus end-tracking proteins (+TIPs) regulate MT growth dynamics and directionality at their plus ends. However, current knowledge about +TIP functions, mostly derived from work in vitro and in nonneuronal cells, may not necessarily apply to the very different context of axonal MTs. For example, the CLIP family of +TIPs are known MT polymerization promoters in nonneuronal cells. However, we show here that neither Drosophila CLIP-190 nor mammalian CLIP-170 is a prominent MT plus end tracker in neurons, which we propose is due to low plus end affinity of the CAP-Gly domain-containing N-terminus and intramolecular inhibition through the C-terminus. Instead, both CLIP-190 and CLIP-170 form F-actin-dependent patches in growth cones, mediated by binding of the coiled-coil domain to myosin-VI. Because our loss-of-function analyses in vivo and in culture failed to reveal axonal roles for CLIP-190, even in double-mutant combinations with four other +TIPs, we propose that CLIP-190 and -170 are not essential axon extension regulators. Our findings demonstrate that +TIP functions known from nonneuronal cells do not necessarily apply to the regulation of the very distinct MT networks in axons.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Robin
authors.initials: R
authors.lastname: Beaven
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
authors.forename: Nikola S
authors.initials: NS
authors.lastname: Dzhindzhev
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Ines
authors.initials: I
authors.lastname: Hahn
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Federico
authors.initials: F
authors.lastname: Dajas-Bailador
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohkura
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom Andreas.Prokop@manchester.ac.uk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokop
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C110769:cytoplasmic linker protein 190; C089785:myosin VI; C076744:cytoplasmic linker protein 170; D018995:Myosin Heavy Chains