Drosophila CLIP-190 and mammalian CLIP-170 display reduced microtubule plus end association in the nervous system

Robin Beaven, N S Dzhindzhev, Yue Qu, I Hahn, Federico Dajas-Bailador, H Ohkura, A Prokop

    Research output: Contribution to journalArticlepeer-review


    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 non-neuronal 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 non-neuronal cells. However, we show here that neither Drosophila CLIP-190 nor mammalian CLIP-170 are prominent MT plus end trackers 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. Since 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 non-neuronal cells do not necessarily apply to the regulation of the very distinct MT networks in axons.
    Original languageEnglish
    Pages (from-to)1491-1508
    Number of pages18
    JournalMol Biol Cell
    Issue number16
    Publication statusPublished - 2015


    • Drosophila, microtubules, axons, neurodevelopment


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