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

Robin Beaven, Nikola S. Dzhindzhev, Yue Qu, Ines Hahn, Federico Dajas-Bailador, Hiroyuki Ohkura, Andreas Prokop*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)1491-1508
Number of pages18
JournalMolecular Biology of the Cell
Volume26
Issue number8
Early online date18 Feb 2015
DOIs
Publication statusPublished - 15 Apr 2015

Fingerprint

Dive into the research topics of 'Drosophila CLIP-190 and mammalian CLIP-170 display reduced microtubule plus end association in the nervous system'. Together they form a unique fingerprint.

Cite this