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Binary Function of ARL3-GTP Revealed by Gene Knockouts

  • Christin Hanke-GogokhiaEmail author
  • Jeanne M. Frederick
  • Houbin Zhang
  • Wolfgang BaehrEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1074)

Abstract

UNC119 and PDEδ are lipid-binding proteins and are thought to form diffusible complexes with transducin-α and prenylated OS proteins, respectively, to mediate their trafficking to photoreceptor outer segments. Here, we investigate mechanisms of trafficking which are controlled by Arf-like protein 3 (Arl3), a small GTPase. The activity of ARL3 is regulated by a GEF (ARL13b) and a GAP (RP2). In a mouse germline knockout of RP2, ARL3-GTP is abundant as its intrinsic GTPase activity is extremely low. High levels of ARL3-GTP impair binding and trafficking of cargo to the outer segment. Germline knockout of ARL3 is embryonically lethal generating a syndromic ciliopathy-like phenotype. Retina- and rod-specific knockout of ARL3 allow to determine the precise mechanisms leading to photoreceptor degeneration. The knockouts reveal binary functions of ARL3-GTP as a key molecule in late-stage photoreceptor ciliogenesis and cargo displacement factor.

Keywords

ARL3 ARL13b PDEδ UNC119 RP2 Photoreceptor Germline knockout Retina disease 

Notes

Acknowledgments

This research was supported by a National Eye Institute grants EY08123, EY019298 (WB), EY014800-039003 (NEI core grant), unrestricted grants to the Departments of Ophthalmology at the University of Utah from Research to Prevent Blindness (RPB; New York), the Retina Research Foundation, Houston (Alice McPherson, MD), and the Foundation for Retina Research (David Brint, MD). WB is a recipient of a Research to Prevent Blindness Senior Investigator and Nelson Trust Award.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Ophthalmology and Visual SciencesJohn A. Moran Eye Center, University of Utah School of MedicineSalt Lake CityUSA
  2. 2.Department of Biochemistry and BiologyUniversity of PotsdamPotsdamGermany
  3. 3.The Sichuan Provincial Key Laboratory for Human Disease Gene StudyThe Institute of Laboratory Medicine, Hospital of University of Electronic Science and Technology of China and Sichuan Provincial People’s HospitalChengduChina
  4. 4.School of Medicine, University of Electronic Science and Technology of ChinaChengduChina
  5. 5.Department of Neurobiology and AnatomyUniversity of Utah School of MedicineSalt Lake CityUSA
  6. 6.Department of BiologyUniversity of UtahSalt Lake CityUSA

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