RRC ID 36280
Author Okumura M, Sakuma C, Miura M, Chihara T.
Title Linking cell surface receptors to microtubules: tubulin folding cofactor D mediates Dscam functions during neuronal morphogenesis.
Journal J Neurosci
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.
Volume 35(5)
Pages 1979-90
Published 2015-2-4
DOI 10.1523/JNEUROSCI.0973-14.2015
PII 35/5/1979
PMID 25653356
PMC PMC6705359
MeSH Amino Acid Sequence Animals Axons / metabolism Binding Sites Cell Adhesion Molecules / chemistry Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism* Cells, Cultured Dendrites / metabolism Drosophila / embryology Drosophila / metabolism Drosophila / physiology Drosophila Proteins / chemistry Drosophila Proteins / genetics Drosophila Proteins / metabolism* Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism* Microtubules / metabolism* Molecular Sequence Data Neurogenesis* Protein Binding Sensory Receptor Cells / cytology Sensory Receptor Cells / metabolism
IF 5.674
Times Cited 19