A Charcot-Marie-Tooth-associated dynamin mutation causes peripheral neuropathy-like phenotypes via Patronin/CAMSAP-dependent microtubule stabilization

A CRISPR knock-in of the Drosophila shi549{Delta}3 dynamin-2-551{Delta}3 variant causes progressive motor impairment and neuromuscular synaptic overgrowth linked to excessive microtubule stabilization.

• Why it matters: Dynamin-2 mutations are linked to Charcot-Marie-Tooth neuropathy, but their in vivo effects on neuronal function and the underlying cellular mechanism remain unclear.
• What they did: The study created a Drosophila model with the shi549{Delta}3 knock-in and assessed physiology at the neuromuscular junction, then used genetic interaction tests by reducing Patronin and performed CAMSAP2 knockdown in mammalian cells.
• The result: Patronin reduction partially suppressed lethality and motor defects, and CAMSAP2 knockdown attenuated dynamin-2-induced microtubule acetylation, supporting a conserved Patronin/CAMSAP-dependent mechanism for neuropathy-like phenotypes.

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