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Mol Biol Cell. 2015 Apr 15;26(8):1491-508. doi: 10.1091/mbc.E14-06-1083. Epub 2015 Feb 18.

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

Author information

1
Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom.
2
Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
3
Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom Andreas.Prokop@manchester.ac.uk.

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.

PMID:
25694447
PMCID:
PMC4395129
DOI:
10.1091/mbc.E14-06-1083
[Indexed for MEDLINE]
Free PMC Article

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