ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure
| Autor: | Andrew F.X. Goldberg, Tanya L. Dilan, Abigail R. Moye, Ratnesh K. Singh, Victoria A. Kimler, Visvanathan Ramamurthy, Daniella Munezero, Thamaraiselvi Saravanan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Axoneme Light Signal Transduction genetic structures Cell Survival Morphogenesis Biology 03 medical and health sciences 0302 clinical medicine Microtubule Retinitis pigmentosa medicine Animals Amino Acid Sequence Cilia Molecular Biology Mice Knockout Cilium A protein Membrane Transport Proteins Cell Biology medicine.disease Retinal Photoreceptor Cell Outer Segment eye diseases Cell biology Mice Inbred C57BL 030104 developmental biology sense organs Segment structure Carrier Proteins 030217 neurology & neurosurgery Retinitis Pigmentosa Visual phototransduction Transcription Factors |
| Zdroj: | Molecular biology of the cell. 29(13) |
| ISSN: | 1939-4586 |
| Popis: | The outer segment (OS) of photoreceptor cells is an elaboration of a primary cilium with organized stacks of membranous disks that contain the proteins needed for phototransduction and vision. Though ciliary formation and function has been well characterized, little is known about the role of cilia in the development of photoreceptor OS. Nevertheless, progress has been made by studying mutations in ciliary proteins, which often result in malformed OSs and lead to blinding diseases. To investigate how ciliary proteins contribute to OS formation, we generated a knockout (KO) mouse model for ARL2BP, a ciliary protein linked to retinitis pigmentosa. The KO mice display an early and progressive reduction in visual response. Before photoreceptor degeneration, we observed disorganization of the photoreceptor OS, with vertically aligned disks and shortened axonemes. Interestingly, ciliary doublet microtubule (MT) structure was also impaired, displaying open B-tubule doublets, paired with loss of singlet MTs. On the basis of results from this study, we conclude that ARL2BP is necessary for photoreceptor ciliary doublet formation and axoneme elongation, which is required for OS morphogenesis and vision. |
| Databáze: | OpenAIRE |
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