Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling
Copyright policy )Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling
Significance Endocrine-cerebro-osteodysplasia (ECO) syndrome, a human genetic disorder affecting multiple organs, is caused by a mutation in intestinal cell kinase ( Ick ) gene. In algae and invertebrates, ICK homologs are known to be associated with ciliary formation. However, it is unclear whether this role of ICK is conserved in mammals and whether clinical symptoms of ECO syndrome are caused by ciliary defects. In this study, using in vivo and in vitro approaches, we found that abnormal ICK function indeed resulted in defective cilia, leading to abnormal Hedgehog signaling. Our results suggest that the role of ICK in ciliogenesis may be highly conserved throughout evolution and that ECO syndrome may be categorized as a ciliopathy, an increasingly recognized class of human genetic disorders.
- Yonsei University Korea (Republic of)
- Dongguk University Korea (Republic of)
- University of Georgia Georgia
- University of Georgia Press United States
- Yonsei University Medical Library Korea (Republic of)
Gli2, Cilia/metabolism*, Inbred C57BL, Mice, Endocrine System/pathology, Protein-Serine-Threonine Kinases/metabolism*, Cerebral Cortex/embryology, Musculoskeletal System, Multiple/pathology*, Smoothened, Cerebral Cortex, Mice, Knockout, Microscopy, Microscopy, Confocal, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Hedgehog Proteins/genetics, Syndrome, Mammalian/metabolism, Mammalian/abnormalities, Embryo, Confocal, Multiple/genetics, MRK, RNA Interference, Body Patterning/physiology, Abnormalities, Western, Cerebral Cortex/pathology, Signal Transduction, Musculoskeletal System/embryology, Knockout, Protein-Serine-Threonine Kinases/genetics, Blotting, Western, 610, Endocrine System, Protein Serine-Threonine Kinases, Electron, Cilia/genetics, Endocrine System/embryology, Hedgehog Proteins/metabolism*, Musculoskeletal System/pathology, Animals, Abnormalities, Multiple, Hedgehog Proteins, Cilia, Body Patterning, Embryo, Mammalian, Body Patterning/genetics, Mice, Inbred C57BL, Microscopy, Electron, ciliopathy, LF4, Signal Transduction/physiology*, Mammalian/ultrastructure, NIH 3T3 Cells, Signal Transduction/genetics
Gli2, Cilia/metabolism*, Inbred C57BL, Mice, Endocrine System/pathology, Protein-Serine-Threonine Kinases/metabolism*, Cerebral Cortex/embryology, Musculoskeletal System, Multiple/pathology*, Smoothened, Cerebral Cortex, Mice, Knockout, Microscopy, Microscopy, Confocal, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Hedgehog Proteins/genetics, Syndrome, Mammalian/metabolism, Mammalian/abnormalities, Embryo, Confocal, Multiple/genetics, MRK, RNA Interference, Body Patterning/physiology, Abnormalities, Western, Cerebral Cortex/pathology, Signal Transduction, Musculoskeletal System/embryology, Knockout, Protein-Serine-Threonine Kinases/genetics, Blotting, Western, 610, Endocrine System, Protein Serine-Threonine Kinases, Electron, Cilia/genetics, Endocrine System/embryology, Hedgehog Proteins/metabolism*, Musculoskeletal System/pathology, Animals, Abnormalities, Multiple, Hedgehog Proteins, Cilia, Body Patterning, Embryo, Mammalian, Body Patterning/genetics, Mice, Inbred C57BL, Microscopy, Electron, ciliopathy, LF4, Signal Transduction/physiology*, Mammalian/ultrastructure, NIH 3T3 Cells, Signal Transduction/genetics
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