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
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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