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Abstract / Description of output
The KMN (Knl1/Mis12/Ndc80) network at the kinetochore, primarily known for its role in chromosome segregation, has been shown to be repurposed during neurodevelopment. Here, we investigate the underlying neuronal mechanism and show that the KMN network promotes the proper axonal organization within the C. elegans head nervous system. Postmitotic degradation of KNL-1, which acts as a scaffold for signaling and has microtubule-binding activities at the kinetochore, led to disorganized ganglia and aberrant placement and organization of axons in the nerve ring - an interconnected axonal network. Through gene-replacement approaches, we demonstrate that the signaling motifs within KNL-1, responsible for recruiting protein phosphatase 1, and activating the spindle assembly checkpoint are required for neurodevelopment. Interestingly, while the microtubule-binding activity is crucial to KMN?s neuronal function, microtubule dynamics and organization were unaffected in the absence of KNL-1. Instead, the NDC-80 microtubule-binding mutant displayed notable defects in axon bundling during nerve ring formation, indicating its role in facilitating axon-axon contacts. Overall, these findings provide evidence for a noncanonical role for the KMN network in shaping the structure and connectivity of the nervous system in C. elegans during brain development.
Original language | English |
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Article number | 35:ar83 |
Number of pages | 14 |
Journal | Molecular Biology of the Cell |
Volume | 35 |
Issue number | 6 |
Early online date | 20 May 2024 |
DOIs | |
Publication status | Published - 1 Jun 2024 |
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Dive into the research topics of 'The outer kinetochore components KNL-1 and Ndc80 complex regulate axon and neuronal cell body positioning in the C. elegans nervous system: Molecular Biology of the Cell'. Together they form a unique fingerprint.Projects
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Molecular mechanisms driving the formation of the neuronal microtubule cytoskeleton
Cheerambathur, D. & Tollervey, D.
1/05/18 → 24/08/23
Project: Research