Department of Radiology; Program in Molecular Medicine; Electron Microscopy Core; Department of Animal Medicine
Cellular and Molecular Physiology | Genetics and Genomics
Arf4 is proposed to be a critical regulator of membrane protein trafficking in early secretory pathway. More recently, Arf4 was also implicated in regulating ciliary trafficking, however, this has not been comprehensively tested in vivo. To directly address Arf4's role in ciliary transport, we deleted Arf4 specifically in either rod photoreceptor cells, kidney, or globally during the early postnatal period. Arf4 deletion in photoreceptors did not cause protein mislocalization or retinal degeneration, as expected if Arf4 played a role in protein transport to the ciliary outer segment. Likewise, Arf4 deletion in kidney did not cause cystic disease, as expected if Arf4 were involved in general ciliary trafficking. In contrast, global Arf4 deletion in the early postnatal period resulted in growth restriction, severe pancreatic degeneration and early death. These findings are consistent with Arf4 playing a critical role in endomembrane trafficking, particularly in the pancreas, but not in ciliary function.
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Citation: PLoS Genet. 2017 Apr 14;13(4):e1006740. eCollection 2017 Apr. Link to article on publisher's site
Pearring, Jillian N.; San Agustin, Jovenal T.; Lobanova, Ekaterina S.; Gabriel, Christopher J.; Lieu, Eric C.; Monis, William J.; Stuck, Michael W.; Strittmatter, Lara; Jaber, Samer M.; Arshavsky, Vadim Y.; and Pazour, Gregory J., "Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration" (2017). Radiology Publications and Presentations. 332.
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