June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
ARL3 regulates transport of prenylated and acylated proteins to photoreceptor outer segment in mouse retina
Author Affiliations & Notes
  • Christin Hanke-Gogokhia
    Ophthalmology, University of Utah, Salt Lake City, UT
    Biochemistry and Biology, University of Potsdam, Potsdam, Germany
  • Jeanne M Frederick
    Ophthalmology, University of Utah, Salt Lake City, UT
  • Houbin Zhang
    School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
  • Wolfgang Baehr
    Ophthalmology, University of Utah, Salt Lake City, UT
  • Footnotes
    Commercial Relationships Christin Hanke-Gogokhia, None; Jeanne Frederick, None; Houbin Zhang, None; Wolfgang Baehr, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1321. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Christin Hanke-Gogokhia, Jeanne M Frederick, Houbin Zhang, Wolfgang Baehr; ARL3 regulates transport of prenylated and acylated proteins to photoreceptor outer segment in mouse retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1321.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: Based on in-vitro experiments, ARL3 (Arf-like protein 3) functions as a GDF (GDI displacement factor) for lipidated proteins. We generated photoreceptor- and retina-specific Arl3 deletions to investigate the function of ARL3 with focus on trafficking of lipidated proteins.

Methods: We generated Arl3+/GT mice containing a EUCOMM gene trap (GT) in intron 1 of the mouse Arl3 gene. Rod- and retina-specific Arl3 conditional knockout mice were obtained by crossing with Flp-mice, followed by iCre75+ and Six3Cre+ transgenics. Photoreceptor function was measured by ERG and progress of retinal degeneration among littermate mice was ascertained by optical coherence tomography, confocal immunohistochemistry and histology.

Results: ERGs and retina histology of PN15 rod-specific knockout mice were indistinguishable from those of the WT littermates, suggesting normal photoreceptor development. OCT revealed rapid photoreceptor loss in retinas of Arl3flox/flox; iCre75+ mice after PN15. At PN20, scotopic ERG a-wave amplitudes were reduced 70-80% with the photopic ERG unaffected. In retinas of 1 month-old knockout mice, scotopic ERGs were extinguished and cone ERGs were attenuated; histology showed 4-5 rows of nuclei in the ONL. The 2 month-old Arl3flox/flox; iCre75+ retina was ~100 μm thinner and only one ONL row, presumably of cone nuclei, was present. Six3Cre+-mediated knockout of Arl3, deleting ARL3 during embryonic retina development, revealed enhanced photoreceptor degeneration: PN20 scotopic (↓80-90%) and photopic (↓70-80%) ERGs were reduced significantly, and OCT at PN15 confirmed faster retina degeneration with much thinner retina of Six3Cre+ knockout than iCre75+. Immunohistochemistry performed using retina sections of PN15 and 1 month-old rod- and retina-specific knockout mice revealed that rhodopsin, GC1 and CNGA1/3 trafficking appear normal. In contrast, prenylated PDE6 and GRK1, and acylated transducin-α mislocalize in the IS and ONL.

Conclusions: Rod- and retina-specific knockout of Arl3 revealed a rapidly-progressing rod degeneration followed by cone defects, resembling RP. Absence of ARL3 impaired the trafficking of peripheral membrane proteins, but not transmembrane proteins, consistent with its function as a GDF.


This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.