Journal
CELLS
Volume 10, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/cells10081885
Keywords
cilium; dynein; intraflagellar transport; primary ciliary dyskinesia; short rib polydactyly syndrome
Categories
Funding
- Radboudumc Hypatia tenure track funding scheme
- European Research Council (ERC) [716344]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [431984000-SFB 1453]
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The function of cilia is crucial for vertebrate development and health, and dysfunction can lead to various ciliopathies. Major human ciliopathy cases are caused by malfunction of ciliary dynein motor activity, with different types of dynein dysfunction resulting in different disease phenotypes.
Although ubiquitously present, the relevance of cilia for vertebrate development and health has long been underrated. However, the aberration or dysfunction of ciliary structures or components results in a large heterogeneous group of disorders in mammals, termed ciliopathies. The majority of human ciliopathy cases are caused by malfunction of the ciliary dynein motor activity, powering retrograde intraflagellar transport (enabled by the cytoplasmic dynein-2 complex) or axonemal movement (axonemal dynein complexes). Despite a partially shared evolutionary developmental path and shared ciliary localization, the cytoplasmic dynein-2 and axonemal dynein functions are markedly different: while cytoplasmic dynein-2 complex dysfunction results in an ultra-rare syndromal skeleto-renal phenotype with a high lethality, axonemal dynein dysfunction is associated with a motile cilia dysfunction disorder, primary ciliary dyskinesia (PCD) or Kartagener syndrome, causing recurrent airway infection, degenerative lung disease, laterality defects, and infertility. In this review, we provide an overview of ciliary dynein complex compositions, their functions, clinical disease hallmarks of ciliary dynein disorders, presumed underlying pathomechanisms, and novel developments in the field.
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