Dendrite shape impacts functional connectivity and is mediated by organization and dynamics of cytoskeletal fibers. Identifying molecular factors that regulate dendritic cytoskeletal architecture is therefore important in understanding mechanistic links between cytoskeletal organization and neuronal function. We identified Formin3 (Form3) as a critical regulator of cytoskeletal architecture in nociceptive sensory neurons in Drosophila larvae. Time course analyses reveal Form3 is cell-autonomously required to promote dendritic arbor complexity. We show that form3 is required for the maintenance of a population of stable dendritic microtubules (MTs), and mutants exhibit defects in the localization of dendritic mitochondria, satellite Golgi, and the TRPA channel Painless. Form3 directly interacts with MTs via FH1-FH2 domains. Mutations in human Inverted Formin 2 (INF2; ortholog of form3) have been causally linked to Charcot-Marie-Tooth (CMT) disease. CMT sensory neuropathies lead to impaired peripheral sensitivity. Defects in form3 function in nociceptive neurons result in severe impairment of noxious heat-evoked behaviors. Expression of the INF2 FH1-FH2 domains partially recovers form3 defects in MTs and nocifensive behavior, suggesting conserved functions, thereby providing putative mechanistic insights into potential etiologies of CMT sensory neuropathies.
Formin3 directs dendritic architecture via microtubule regulation and is required for somatosensory nociceptive behavior
These authors contributed equally to this work
- Award Group:
- Funder(s): National Institute of Neurological Disorders and Stroke
- Award Id(s): NS086082
- Funder(s):
- Award Group:
- Funder(s): National Science Foundation
- Award Id(s): DBI-1546335
- Funder(s):
- Award Group:
- Funder(s): magyar Tudományos Akadémia
- Award Id(s): KTIA_NAP_1302-2014-0007
- Funder(s):
- Award Group:
- Funder(s): Hungarian Scientific Research Fund
- Award Id(s): GINOP-2.3.2-15-2016-00032
- Funder(s):
- Award Group:
- Funder(s): Hungarian Scientific Research Fund
- Award Id(s): PD 128357
- Funder(s):
Currently Viewing Accepted Manuscript - Newer Version Available
Ravi Das, Shatabdi Bhattacharjee, Jamin M. Letcher, Jenna M. Harris, Sumit Nanda, Istvan Foldi, Erin N. Lottes, Hansley M. Bobo, Benjamin D. Grantier, József Mihály, Giorgio A. Ascoli, Daniel N. Cox; Formin3 directs dendritic architecture via microtubule regulation and is required for somatosensory nociceptive behavior. Development 2021; dev.187609. doi: https://doi.org/10.1242/dev.187609
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