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Okumura, M., Sakuma, C., Miura, M., Chihara, T. (2015). Linking Cell Surface Receptors to Microtubules: Tubulin Folding Cofactor D Mediates Dscam Functions during Neuronal Morphogenesis.  J. Neurosci. 35(5): 1979--1990.
FlyBase ID
FBrf0227472
Publication Type
Research paper
Abstract

Formation of functional neural networks requires the coordination of cell surface receptors and downstream signaling cascades, which eventually leads to dynamic remodeling of the cytoskeleton. Although a number of guidance receptors affecting actin cytoskeleton remodeling have been identified, it is relatively unknown how microtubule dynamics are regulated by guidance receptors. We used Drosophila olfactory projection neurons to study the molecular mechanisms of neuronal morphogenesis. Dendrites of each projection neuron target a single glomerulus of ∼50 glomeruli in the antennal lobe, and the axons show stereotypical pattern of terminal arborization. In the course of genetic analysis of the dachsous mutant allele (ds(UAO71)), we identified a mutation in the tubulin folding cofactor D gene (TBCD) as a background mutation. TBCD is one of five tubulin-folding cofactors required for the formation of α- and β-tubulin heterodimers. Single-cell clones of projection neurons homozygous for the TBCD mutation displayed disruption of microtubules, resulting in ectopic arborization of dendrites, and axon degeneration. Interestingly, overexpression of TBCD also resulted in microtubule disruption and ectopic dendrite arborization, suggesting that an optimum level of TBCD is crucial for in vivo neuronal morphogenesis. We further found that TBCD physically interacts with the intracellular domain of Down syndrome cell adhesion molecule (Dscam), which is important for neural development and has been implicated in Down syndrome. Genetic analyses revealed that TBCD cooperates with Dscam in vivo. Our study may offer new insights into the molecular mechanism underlying the altered neural networks in cognitive disabilities of Down syndrome.

PubMed ID
PubMed Central ID
PMC6705359 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Neurosci.
    Title
    Journal of Neuroscience
    Publication Year
    1981-
    ISBN/ISSN
    0270-6474 1529-2401
    Data From Reference