The Drosophila fragile X mental retardation protein modulates the neuronal cytoskeleton to limit dendritic arborization.

TitleThe Drosophila fragile X mental retardation protein modulates the neuronal cytoskeleton to limit dendritic arborization.
Publication TypeJournal Article
Year of Publication2022
AuthorsLi, H, Gavis, ER
JournalDevelopment
Volume149
Issue10
Date Published2022 May 15
ISSN1477-9129
KeywordsAnimals, Cytoskeleton, Drosophila, Fragile X Mental Retardation Protein, Microtubules, Neuronal Plasticity, RNA, Messenger
Abstract

<p>Dendritic arbor development is a complex, highly regulated process. Post-transcriptional regulation mediated by RNA-binding proteins plays an important role in neuronal dendrite morphogenesis by delivering on-site, on-demand protein synthesis. Here, we show how the Drosophila fragile X mental retardation protein (FMRP), a conserved RNA-binding protein, limits dendrite branching to ensure proper neuronal function during larval sensory neuron development. FMRP knockdown causes increased dendritic terminal branch growth and a resulting overelaboration defect due, in part, to altered microtubule stability and dynamics. FMRP also controls dendrite outgrowth by regulating the Drosophila profilin homolog chickadee (chic). FMRP colocalizes with chic mRNA in dendritic granules and regulates its dendritic localization and protein expression. Whereas RNA-binding domains KH1 and KH2 are both crucial for FMRP-mediated dendritic regulation, KH2 specifically is required for FMRP granule formation and chic mRNA association, suggesting a link between dendritic FMRP granules and FMRP function in dendrite elaboration. Our studies implicate FMRP-mediated modulation of both the neuronal microtubule and actin cytoskeletons in multidendritic neuronal architecture, and provide molecular insight into FMRP granule formation and its relevance to FMRP function in dendritic patterning.</p>

DOI10.1242/dev.200379
Alternate JournalDevelopment
PubMed ID35502752
Grant ListChina Scholarship Council Memorandum of Understanding with Princeton University dated April 1, 2015 / / China Scholarship Council /
/ / China Scholarship Council /
/ / Princeton University /