PUBLICATION
Coupling of dynamic microtubules to F-actin by Fmn2 regulates chemotaxis of neuronal growth cones
- Authors
- Kundu, T., Dutta, P., Nagar, D., Maiti, S., Ghose, A.
- ID
- ZDB-PUB-210729-12
- Date
- 2021
- Source
- Journal of Cell Science 134(13): (Journal)
- Registered Authors
- Ghose, Aurnab
- Keywords
- Actin–microtubule crosstalk, Axon guidance, Filopodia, Fmn2, Formin-2, Growth cone
- MeSH Terms
-
- Actin Cytoskeleton
- Actins*
- Animals
- Axons
- Chemotaxis*
- Chickens
- Formins/genetics*
- Growth Cones*
- Microtubules
- Neurons/cytology*
- Zebrafish
- PubMed
- 34313311 Full text @ J. Cell Sci.
Citation
Kundu, T., Dutta, P., Nagar, D., Maiti, S., Ghose, A. (2021) Coupling of dynamic microtubules to F-actin by Fmn2 regulates chemotaxis of neuronal growth cones. Journal of Cell Science. 134(13):.
Abstract
Dynamic co-regulation of the actin and microtubule subsystems enables the highly precise and adaptive remodelling of the cytoskeleton necessary for critical cellular processes, such as axonal pathfinding. The modes and mediators of this interpolymer crosstalk, however, are inadequately understood. We identify Fmn2, a non-diaphanous-related formin associated with cognitive disabilities, as a novel regulator of cooperative actin-microtubule remodelling in growth cones of both chick and zebrafish neurons. We show that Fmn2 stabilizes microtubules in the growth cones of cultured spinal neurons and in vivo. Super-resolution imaging revealed that Fmn2 facilitates guidance of exploratory microtubules along actin bundles into the chemosensory filopodia. Using live imaging, biochemistry and single-molecule assays, we show that a C-terminal domain in Fmn2 is necessary for the dynamic association between microtubules and actin filaments. In the absence of the cross-bridging function of Fmn2, filopodial capture of microtubules is compromised, resulting in destabilized filopodial protrusions and deficits in growth cone chemotaxis. Our results uncover a critical function for Fmn2 in actin-microtubule crosstalk in neurons and demonstrate that the modulation of microtubule dynamics via associations with F-actin is central to directional motility.
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