Formin 3 Directs Dendritic Architecture via Microtubule Regulation and is Required for Somatosensory Nociceptive Behavior

Das, Ravi and Bhattacharjee, Shatabdi and Letcher, Jamin M. and Harris, Jenna M. and Nanda, Sumit and Földi, István and Mihály, József (2021) Formin 3 Directs Dendritic Architecture via Microtubule Regulation and is Required for Somatosensory Nociceptive Behavior. DEVELOPMENT, 148 (16). pp. 1-19. ISSN 0950-1991 (print); 1477-9129 (online)

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Abstract

Dendrite shape impacts functional connectivity and is mediated by organization and dynamics of cytoskeletal fibers. Identifying the molecular factors that regulate dendritic cytoskeletal architecture is therefore important in understanding the mechanistic links between cytoskeletal organization and neuronal function. We identified Formin 3 (Form3) as an essential regulator of cytoskeletal architecture in nociceptive sensory neurons in Drosophila larvae. Time course analyses reveal that 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; orthologof 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 heatevoked 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.

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