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J Cell Sci. 2017 Aug 1;130(15):2506-2519. doi: 10.1242/jcs.203455. Epub 2017 Jun 12.

The formin DAAM is required for coordination of the actin and microtubule cytoskeleton in axonal growth cones.

Author information

1
Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, MTA-SZBK NAP B Axon Growth and Regeneration Group, Temesvári krt. 62, Szeged H-6726, Hungary.
2
University of Pécs, Medical School, Department of Biophysics, Szigeti str. 12, Pécs H-7624, Hungary.
3
Szentágothai Research Center, Ifjúság str. 34, Pécs H-7624, Hungary.
4
MTA-SZTE Translational Gastroenterology Research Group, First Department of Internal Medicine, Szeged H-6720, Hungary.
5
Institute for Translational Medicine, Department of Pathophysiology, University of Pécs, Pécs H-7624, Hungary.
6
Institute for Translational Medicine, Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool L69 3BX, UK.
7
Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, MTA-SZBK NAP B Axon Growth and Regeneration Group, Temesvári krt. 62, Szeged H-6726, Hungary mihaly.jozsef@brc.mta.hu.

Abstract

Directed axonal growth depends on correct coordination of the actin and microtubule cytoskeleton in the growth cone. However, despite the relatively large number of proteins implicated in actin-microtubule crosstalk, the mechanisms whereby actin polymerization is coupled to microtubule stabilization and advancement in the peripheral growth cone remained largely unclear. Here, we identified the formin Dishevelled-associated activator of morphogenesis (DAAM) as a novel factor playing a role in concerted regulation of actin and microtubule remodeling in Drosophilamelanogaster primary neurons. In vitro, DAAM binds to F-actin as well as to microtubules and has the ability to crosslink the two filament systems. Accordingly, DAAM associates with the neuronal cytoskeleton, and a significant fraction of DAAM accumulates at places where the actin filaments overlap with that of microtubules. Loss of DAAM affects growth cone and microtubule morphology, and several aspects of microtubule dynamics; and biochemical and cellular assays revealed a microtubule stabilization activity and binding to the microtubule tip protein EB1. Together, these data suggest that, besides operating as an actin assembly factor, DAAM is involved in linking actin remodeling in filopodia to microtubule stabilization during axonal growth.

KEYWORDS:

Actin; DAAM; Drosophila; Formin; Growth cone; Microtubule

PMID:
28606990
DOI:
10.1242/jcs.203455
[Indexed for MEDLINE]
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