Ciliopathy patient variants reveal organelle-specific functions for TUBB4B in axonemal microtubules
Ciliopathies
Centriole
Ciliopathy
Ciliogenesis
Basal body
Intraflagellar Transport
Organelle
DOI:
10.1126/science.adf5489
Publication Date:
2024-04-25T18:00:04Z
AUTHORS (84)
ABSTRACT
Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct form cell type– and context-specific microtubule structures is poorly understood. Based on a cohort 12 patients with primary ciliary dyskinesia as well mouse mutants, we identified characterized variants TUBB4B isotype that specifically perturbed centriole cilium biogenesis. Distinct differentially affected dynamics cilia formation dominant-negative manner. Structure-function studies revealed disrupted tubulin interfaces, thereby enabling stratification into three classes ciliopathic diseases. These findings show specific have nonredundant subcellular functions establish link between tubulinopathies ciliopathies.
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