PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Citation - WoS: 2Citation - Scopus: 2ARL13B Regulates Juxtaposed Cilia-Cilia Elongation in BBSome Dependent Manner in Caenorhabditis Elegans(Cell Press, 2025-02) Turan, Merve Gul; Kantarci, Hanife; Cevik, Sebiha; Kaplan, Oktay I.The interaction of cilia with various cellular compartments, such as axons, has emerged as a new form of cellular communication. Cilia often extend in proximity to cilia from neighboring cells. However, the mechanisms driving this process termed juxtaposed cilia-cilia elongation (JCE) remain unclear. We use fluorescence-based visualization to study the mechanisms of coordinated cilia elongation in sensory neurons of Caenorhabditis elegans. Conducting a selective gene-based screening strategy reveals that ARL-13/ARL13B and MKS-5/RPGRIP1L are essential for JCE. We demonstrate that ARL-13 modulates JCE independently of cilia length. Loss of NPHP-2/inversin along with HDAC-6 enhances the cilia misdirection phenotype of arl-13 mutants, while disruption of the BBSome complex, but not microtubule components, partially suppresses the JCE defects in arl-13 mutants. We further show changes in the phospholipid compositions in arl-13 mutants. We suggest that ARL-13 contributes to JCE, in part, through the modulation of the ciliary membrane.Article Citation - WoS: 1Citation - Scopus: 1A Homozygous Frameshift Variant in the CILK1 Gene Causes Cranioectodermal Dysplasia(Springernature, 2025-07-04) Sezer, Abdullah; Oner, Sukru S.; Saat, Hanife; Turan, Merve G.; Gungor, Tulin; Cevik, Sebiha; Kaplan, Oktay I.Cranioectodermal dysplasia (CED) is a ciliopathy characterized by skeletal and ectodermal abnormalities, renal failure, and liver fibrosis. Pathogenic variants in genes that encode the intraflagellar transport (IFT) complex components, particularly IFT-A, are responsible for approximately two-thirds of the CED cases. However, the cause of the remaining cases remains unknown. Ciliogenesis-associated kinase 1 (CILK1) is a highly conserved ciliary serine/threonine kinase with an N-terminal catalytic domain responsible for kinase activity and a C-terminal non-catalytic domain that interacts with the IFT-B complex. Biallelic variants in the catalytic domain are associated with lethal skeletal dysplasia, endocrine cerebroosteodysplasia, and short-rib polydactyly syndrome. No human disease has been linked to biallelic variants in the non-catalytic domain. We present a homozygous frameshift variant in the CILK1 gene that affects the distal part of the non-catalytic domain, causing CED in five patients from two pedigrees. All the patients survived into childhood and had disproportionately short stature, skeletal abnormalities, ectodermal dysplasia, renal issues, and liver complications. Functional data from patient-derived cells and the C. elegans model indicate that the variant reduces cilia number, increases cilia length, and disrupts the localization of IFT components. In contrast, the ciliary localization of CILK1 bearing the variant itself remains unaffected. Notably, we rescued the majority of these abnormalities by reintroducing CILK1 into patient-derived cells. Finally, our study describes CILK1 as a novel causal gene and the first non-IFT protein-encoding gene in the etiology of CED, thus expanding the known genotypic, mechanistic, and phenotypic spectrum of CED.