Ciliary Dyneins and Dynein Related Ciliopathies

Cells

Dinu Antony¹  Miriam Schmidts¹  Han G. Brunner² 

[1] Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg University Faculty of Medicine, Mathildenstrasse 1, 79106 Freiburg, Germany;Genome Research Division, Human Genetics Department, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 KL Nijmegen, The Netherlands;

关键词: cilium;    dynein;    intraflagellar transport;    primary ciliary dyskinesia;    short rib polydactyly syndrome;   

DOI  :  10.3390/cells10081885

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown