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Publication : Arf-like Protein 2 (ARL2) Controls Microtubule Neogenesis during Early Postnatal Photoreceptor Development.

First Author  Gerstner CD Year  2022
Journal  Cells Volume  12
Issue  1 PubMed ID  36611941
Mgi Jnum  J:332516 Mgi Id  MGI:7426270
Doi  10.3390/cells12010147 Citation  Gerstner CD, et al. (2022) Arf-like Protein 2 (ARL2) Controls Microtubule Neogenesis during Early Postnatal Photoreceptor Development. Cells 12(1)
abstractText  Arf-like protein 2 (ARL2) is a ubiquitously expressed small GTPase with multiple functions. In a cell culture, ARL2 participates with tubulin cofactor D (TBCD) in the neogenesis of tubulin alphabeta-heterodimers, the building blocks of microtubules. To evaluate this function in the retina, we conditionally deleted ARL2 in mouse retina at two distinct stages, either during the embryonic development ((ret)Arl2(-/-)) or after ciliogenesis specifically in rods ((rod)Arl2(-/-)). (ret)Arl2(-/-) retina sections displayed distorted nuclear layers and a disrupted microtubule cytoskeleton (MTC) as early as postnatal day 6 (P6). Rod and cone outer segments (OS) did not form. By contrast, the rod ARL2 knockouts were stable at postnatal day 35 and revealed normal ERG responses. Cytoplasmic dynein is reduced in (ret)Arl2(-/-) inner segments (IS), suggesting that dynein may be unstable in the absence of a normal MTC. We investigated the microtubular stability in the absence of either ARL2 ((ret)ARL2(-/-)) or DYNC1H1 ((ret)Dync1h1(-/-)), the dynein heavy chain, and found that both the (ret)Arl2(-/-) and (ret)Dync1h1(-/-) retinas exhibited reduced microtubules and nuclear layer distortion. The results suggest that ARL2 and dynein depend on each other to generate a functional MTC during the early photoreceptor development.
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