A human DCC variant causing mirror movement disorder reveals an essential role for the Wave regulatory complex in Netrin/DCC signaling
Chaudhari, K.; Zhang, K.; Yam, P. T.; Zang, Y.; Kramer, D. A.; Schlienger, S.; Calabretta, S.; Collins, M.; Srour, M.; Chen, B.; Charron, F.; Bashaw, G. J.
Show abstract
The axon guidance cue, Netrin-1, signals through its receptor DCC to attract commissural axons to the midline. Pathogenic variants in DCC frequently lead to congenital mirror movements (CMM), but how these variants impact DCC function is largely unknown. Screening of DCC in individuals with CMM recently revealed a novel variant located in a conserved motif in the cytoplasmic tail of DCC that is predicted to bind to a central actin nucleation promoting factor, the WAVE regulatory complex (WRC). Here, we use biochemical and axon guidance assays to show that this CMM-associated DCC variant is pathogenic by disrupting the interaction between DCC and the WRC. This DCC-WRC interaction is evolutionarily conserved and is required for Netrin-1 mediated commissural axon outgrowth and guidance. Together, we identify the WRC as a pivotal component of Netrin-1/DCC signaling and further provide a molecular mechanism explaining how genetic variants in DCC may lead to CMM.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Editing of endogenous tubulins reveals varying effects of tubulin posttranslational modifications on axonal growth and regeneration 96%
- Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex 96%
- Flamingo participates in multiple models of cell competition 96%
Similar papers in this journal
- isoTarget: a genetic method for analyzing the functional diversity of splicing isoforms in vivo 97%
- Affinity Requirements For Control Of Synaptic Targeting And Neuronal Cell Survival By Heterophilic IgSF Cell Adhesion Molecules 97%
- A developmental pathway for epithelial-to-motoneuron transformation in C. elegans 96%
Similar papers in this journal
- Synapsin is required for dense core vesicle capture and cAMP-dependent neuropeptide release 95%
- Drebrin Regulates Collateral Axon Branching in Cortical Layer II/III Somatosensory Neurons 95%
- Structural and functional synaptic plasticity induced by convergent synapse loss requires co-innervation in the Drosophila neuromuscular circuit 95%
Similar papers in this journal
- C. elegans Sine oculis/SIX-type homeobox genes act as homeotic switches to define neuronal subtype identities 95%
- Transcytosis-mediated anterograde transport of TrkA receptors is necessary for sympathetic neuron development and function 95%
- A PAK kinase family member and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration 94%
Similar papers in this journal
- Cilium proteomics reveals Numb as a positive regulator of the Hedgehog signaling pathway 95%
- Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila 95%
- Pegasus, a small extracellular peptide regulating the short-range diffusion of Wingless 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.