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1.
Nat Commun ; 14(1): 7520, 2023 11 18.
Article in English | MEDLINE | ID: mdl-37980357

ABSTRACT

The elimination of synapses during circuit remodeling is critical for brain maturation; however, the molecular mechanisms directing synapse elimination and its timing remain elusive. We show that the transcriptional regulator DVE-1, which shares homology with special AT-rich sequence-binding (SATB) family members previously implicated in human neurodevelopmental disorders, directs the elimination of juvenile synaptic inputs onto remodeling C. elegans GABAergic neurons. Juvenile acetylcholine receptor clusters and apposing presynaptic sites are eliminated during the maturation of wild-type GABAergic neurons but persist into adulthood in dve-1 mutants, producing heightened motor connectivity. DVE-1 localization to GABAergic nuclei is required for synapse elimination, consistent with DVE-1 regulation of transcription. Pathway analysis of putative DVE-1 target genes, proteasome inhibitor, and genetic experiments implicate the ubiquitin-proteasome system in synapse elimination. Together, our findings define a previously unappreciated role for a SATB family member in directing synapse elimination during circuit remodeling, likely through transcriptional regulation of protein degradation processes.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Humans , Caenorhabditis elegans/metabolism , Synapses/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Receptors, Cholinergic/metabolism , GABAergic Neurons/metabolism
2.
J Cell Biol ; 220(9)2021 09 06.
Article in English | MEDLINE | ID: mdl-34137792

ABSTRACT

Neuronal polarization is facilitated by the formation of axons with parallel arrays of plus-end-out and dendrites with the nonuniform orientation of microtubules. In C. elegans, the posterior lateral microtubule (PLM) neuron is bipolar with its two processes growing along the anterior-posterior axis under the guidance of Wnt signaling. Here we found that loss of the Kinesin-13 family microtubule-depolymerizing enzyme KLP-7 led to the ectopic extension of axon-like processes from the PLM cell body. Live imaging of the microtubules and axonal transport revealed mixed polarity of the microtubules in the short posterior process, which is dependent on both KLP-7 and the minus-end binding protein PTRN-1. KLP-7 is positively regulated in the posterior process by planar cell polarity components of Wnt involving rho-1/rock to induce mixed polarity of microtubules, whereas it is negatively regulated in the anterior process by the unc-73/ced-10 cascade to establish a uniform microtubule polarity. Our work elucidates how evolutionarily conserved Wnt signaling establishes the microtubule polarity in neurons through Kinesin-13.


Subject(s)
Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans/genetics , Kinesins/genetics , Microtubule-Associated Proteins/genetics , Microtubules/metabolism , Neurogenesis/genetics , Wnt Signaling Pathway/genetics , Animals , Axons/metabolism , Axons/ultrastructure , Biological Transport , Caenorhabditis elegans/cytology , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/metabolism , Cell Differentiation , Cell Polarity/genetics , Dendrites/metabolism , Dendrites/ultrastructure , Gene Expression Regulation , Kinesins/metabolism , Microtubule-Associated Proteins/metabolism , Microtubules/ultrastructure , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , rac GTP-Binding Proteins/genetics , rac GTP-Binding Proteins/metabolism , rho GTP-Binding Proteins/genetics , rho GTP-Binding Proteins/metabolism , rho-Associated Kinases/genetics , rho-Associated Kinases/metabolism
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