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Deletion of the phosphatase INPP5E in the murine retina impairs photoreceptor axoneme formation and prevents disc morphogenesis.

Publication ,  Journal Article
Sharif, AS; Gerstner, CD; Cady, MA; Arshavsky, VY; Mitchell, C; Ying, G; Frederick, JM; Baehr, W
Published in: J Biol Chem
2021

INPP5E, also known as pharbin, is a ubiquitously expressed phosphatidylinositol polyphosphate 5-phosphatase that is typically located in the primary cilia and modulates the phosphoinositide composition of membranes. Mutations to or loss of INPP5E is associated with ciliary dysfunction. INPP5E missense mutations of the phosphatase catalytic domain cause Joubert syndrome in humans-a syndromic ciliopathy affecting multiple tissues including the brain, liver, kidney, and retina. In contrast to other primary cilia, photoreceptor INPP5E is prominently expressed in the inner segment and connecting cilium and absent in the outer segment, which is a modified primary cilium dedicated to phototransduction. To investigate how loss of INPP5e causes retina degeneration, we generated mice with a retina-specific KO (Inpp5eF/F;Six3Cre, abbreviated as retInpp5e-/-). These mice exhibit a rapidly progressing rod-cone degeneration resembling Leber congenital amaurosis that is nearly completed by postnatal day 21 (P21) in the central retina. Mutant cone outer segments contain vesicles instead of discs as early as P8. Although P10 mutant outer segments contain structural and phototransduction proteins, axonemal structure and disc membranes fail to form. Connecting cilia of retInpp5e-/- rods display accumulation of intraflagellar transport particles A and B at their distal ends, suggesting disrupted intraflagellar transport. Although INPP5E ablation may not prevent delivery of outer segment-specific proteins by means of the photoreceptor secretory pathway, its absence prevents the assembly of axonemal and disc components. Herein, we suggest a model for INPP5E-Leber congenital amaurosis, proposing how deletion of INPP5E may interrupt axoneme extension and disc membrane elaboration.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

2021

Volume

296

Start / End Page

100529

Location

United States

Related Subject Headings

  • Retinal Rod Photoreceptor Cells
  • Retinal Degeneration
  • Retinal Cone Photoreceptor Cells
  • Retina
  • Protein Transport
  • Phosphoric Monoester Hydrolases
  • Morphogenesis
  • Mice, Knockout
  • Mice
  • Eye Proteins
 

Citation

APA
Chicago
ICMJE
MLA
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Sharif, A. S., Gerstner, C. D., Cady, M. A., Arshavsky, V. Y., Mitchell, C., Ying, G., … Baehr, W. (2021). Deletion of the phosphatase INPP5E in the murine retina impairs photoreceptor axoneme formation and prevents disc morphogenesis. J Biol Chem, 296, 100529. https://doi.org/10.1016/j.jbc.2021.100529
Sharif, Ali S., Cecilia D. Gerstner, Martha A. Cady, Vadim Y. Arshavsky, Christina Mitchell, Guoxin Ying, Jeanne M. Frederick, and Wolfgang Baehr. “Deletion of the phosphatase INPP5E in the murine retina impairs photoreceptor axoneme formation and prevents disc morphogenesis.J Biol Chem 296 (2021): 100529. https://doi.org/10.1016/j.jbc.2021.100529.
Sharif AS, Gerstner CD, Cady MA, Arshavsky VY, Mitchell C, Ying G, et al. Deletion of the phosphatase INPP5E in the murine retina impairs photoreceptor axoneme formation and prevents disc morphogenesis. J Biol Chem. 2021;296:100529.
Sharif, Ali S., et al. “Deletion of the phosphatase INPP5E in the murine retina impairs photoreceptor axoneme formation and prevents disc morphogenesis.J Biol Chem, vol. 296, 2021, p. 100529. Pubmed, doi:10.1016/j.jbc.2021.100529.
Sharif AS, Gerstner CD, Cady MA, Arshavsky VY, Mitchell C, Ying G, Frederick JM, Baehr W. Deletion of the phosphatase INPP5E in the murine retina impairs photoreceptor axoneme formation and prevents disc morphogenesis. J Biol Chem. 2021;296:100529.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

2021

Volume

296

Start / End Page

100529

Location

United States

Related Subject Headings

  • Retinal Rod Photoreceptor Cells
  • Retinal Degeneration
  • Retinal Cone Photoreceptor Cells
  • Retina
  • Protein Transport
  • Phosphoric Monoester Hydrolases
  • Morphogenesis
  • Mice, Knockout
  • Mice
  • Eye Proteins