Tubulin autoregulation mediator TTC5 regulates neuronal morphology and migration.

TTC5 loss in iPSC-derived cortical neurons suppresses microtubule polymerization, axonal outgrowth, and arborization while enhancing cellular motility, linking tubulin autoregulation to neuronal morphology.

• Why it matters: Neurons must balance tubulin supply with microtubule dynamics, but how tubulin autoregulation is implemented and how its failure affects development is unclear.
• What they did: The study tested tubulin autoregulation in iPSC-derived cortical neurons and used TTC5 loss and structure-guided TTC5 mutations, plus soluble tubulin manipulation and SCAPER downregulation.
• The result: In mice, TTC5 loss in cortical projection neurons disrupts axon and dendrite arborization and causes hypermigration, and patient-derived TTC5 mutants phenocopy motility dysregulation.

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