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Publication : Mouse ACF7 and drosophila short stop modulate filopodia formation and microtubule organisation during neuronal growth.

First Author  Sanchez-Soriano N Year  2009
Journal  J Cell Sci Volume  122
Issue  Pt 14 Pages  2534-42
PubMed ID  19571116 Mgi Jnum  J:153155
Mgi Id  MGI:4361077 Doi  10.1242/jcs.046268
Citation  Sanchez-Soriano N, et al. (2009) Mouse ACF7 and drosophila short stop modulate filopodia formation and microtubule organisation during neuronal growth. J Cell Sci 122(Pt 14):2534-42
abstractText  Spectraplakins are large actin-microtubule linker molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. Expression data for the mammalian spectraplakin ACF7 and genetic analyses of the Drosophila spectraplakin Short stop (Shot) suggest an important role during neurogenesis. Using three parallel neuronal culture systems we demonstrate that, like Shot, ACF7 is essential for axon extension and describe, for the first time, their subcellular functions during axonal growth. Firstly, both ACF7 and Shot regulate the organisation of neuronal microtubules, a role dependent on both the F-actin- and microtubule-binding domains. This role in microtubule organisation is probably the key mechanism underlying the roles of Shot and ACF7 in growth cone advance. Secondly, we found a novel role for ACF7 and Shot in regulating the actin cytoskeleton through their ability to control the formation of filopodia. This function in F-actin regulation requires EF-hand motifs and interaction with the translational regulator Krasavietz/eIF5C, indicating that the underlying mechanisms are completely different from those used to control microtubules. Our data provide the basis for the first mechanistic explanation for the role of Shot and ACF7 in the developing nervous system and demonstrate their ability to coordinate the organisation of both actin and microtubule networks during axonal growth.
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