Редактирование: ARL13B (раздел)

==Publications==

{{medline-entry
|title=[[ARL13B]], a Joubert Syndrome-Associated Protein, Is Critical for Retinogenesis and Elaboration of Mouse Photoreceptor Outer Segments.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30573647
|abstract=Mutations in the Joubert syndrome-associated small GTPase [[ARL13B]] are linked to photoreceptor impairment and vision loss. To determine the role of [[ARL13B]] in the development, function, and maintenance of ciliated photoreceptors, we generated a pan-retina knock-out ([i]Six3[/i]-Cre) and a rod photoreceptor-specific inducible conditional knock-out ([i]Pde6g[/i]-Cre ) of [[ARL13B]] using murine models. Embryonic deletion of [[ARL13B]] led to defects in retinal development with reduced cell proliferation. In the absence of [[ARL13B]], photoreceptors failed to develop outer segment (OS) membranous discs and axonemes, resulting in loss of function and rapid degeneration. Additionally, the majority of photoreceptor basal bodies did not dock properly at the apical edge of the inner segments. The removal of [[ARL13B]] in adult rod photoreceptor cells after maturation of OS resulted in loss of photoresponse and vesiculation in the OS. Before changes in photoresponse, removal of [[ARL13B]] led to mislocalization of rhodopsin, prenylated phosphodiesterase-6 (PDE6), and intraflagellar transport protein-88 (IFT88). Our findings show that [[ARL13B]] is required at multiple stages of retinogenesis, including early postnatal proliferation of retinal progenitor cells, development of photoreceptor cilia, and morphogenesis of photoreceptor OS discs regardless of sex. Last, our results establish a need for [[ARL13B]] in photoreceptor maintenance and protein trafficking.  The normal development of photoreceptor cilia is essential to create functional, organized outer segments with stacked membrane discs that house the phototransduction proteins necessary for sight. Our study identifies a complex role for [[ARL13B]], a small GTPase linked to Joubert syndrome and visual impairment, at various stages of photoreceptor development. Loss of [[ARL13B]] led to defects in retinal proliferation, altered placement of basal bodies crucial for components of the cilium (transition zone) to emanate, and absence of photoreceptor-stacked discs. These defects led to extinguished visual response and dysregulated protein trafficking. Our findings show the complex role [[ARL13B]] plays in photoreceptor development, viability, and function. Our study accounts for the severe retinal impairment observed in [[ARL13B]]-linked Joubert syndrome patients.
|mesh-terms=* ADP-Ribosylation Factors
* Aging
* Animals
* Axoneme
* Cilia
* Eye Proteins
* Female
* Gene Expression Regulation, Developmental
* Gene Knockout Techniques
* Male
* Mice
* Mice, Inbred C57BL
* Organelle Biogenesis
* Protein Transport
* Retina
* Rod Cell Outer Segment
* Sensory Rhodopsins
|keywords=* IFT
* Joubert syndrome
* blindness
* outer segment
* photoreceptors
* protein trafficking
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381253
}}