Drosophila CLIP-190 and mammalian CLIP-170 display reduced microtubule plus end association in the nervous system
Beaven, Robin and Dzhindzhev, Nikola S. and Qu, Yue and Hahn, Ines and Dajas-Bailador, Federico and Ohkura, Hiroyuki and Prokop, Anderas (2015) Drosophila CLIP-190 and mammalian CLIP-170 display reduced microtubule plus end association in the nervous system. Molecular Biology of the Cell, 26 (8). pp. 1491-1508. ISSN 1939-4586
Official URL: http://www.molbiolcell.org/content/26/8/1491
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.
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