Kundu, Tanushree;
Siva Das, Sooraj;
Sewatkar, Lisas K;
Kumar, Divya S;
Nagar, Dhriti;
Ghose, Aurnab;
(2022)
Antagonistic Activities of Fmn2 and ADF Regulate Axonal F-Actin Patch Dynamics and the Initiation of Collateral Branching.
The Journal of Neuroscience
, 42
(39)
pp. 7355-7369.
10.1523/jneurosci.3107-20.2022.
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Abstract
Interstitial collateral branching of axons is a critical component in the development of functional neural circuits. Axon collateral branches are established through a series of cellular processes initiated by the development of a specialized, focal F-actin network in axons. The formation, maintenance and remodeling of this F-actin patch is critical for the initiation of axonal protrusions that are subsequently consolidated to form a collateral branch. However, the mechanisms regulating F-actin patch dynamics are poorly understood. Fmn2 is a formin family member implicated in multiple neurodevelopmental disorders. We find that Fmn2 regulates the initiation of axon collateral protrusions in chick spinal neurons and in zebrafish motor neurons. Fmn2 localizes to the protrusion-initiating axonal F-actin patches and regulates the lifetime and size of these F-actin networks. The F-actin nucleation activity of Fmn2 is necessary for F-actin patch stability but not for initiating patch formation. We show that Fmn2 insulates the F-actin patches from disassembly by the actin-depolymerizing factor, ADF, and promotes long-lived, larger patches that are competent to initiate axonal protrusions. The regulation of axonal branching can contribute to the neurodevelopmental pathologies associated with Fmn2 and the dynamic antagonism between Fmn2 and ADF may represent a general mechanism of formin-dependent protection of Arp2/3-initiated F-actin networks from disassembly.
| Type: | Article |
|---|---|
| Title: | Antagonistic Activities of Fmn2 and ADF Regulate Axonal F-Actin Patch Dynamics and the Initiation of Collateral Branching |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1523/jneurosci.3107-20.2022 |
| Publisher version: | https://doi.org/10.1523/jneurosci.3107-20.2022 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | ADF; axon collateral branching; cytoskeleton; F-actin patch; Fmn2; formins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10204106 |
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