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Large-Scale Purification of Porcine or Bovine Photoreceptor Outer Segments for Phagocytosis Assays on Retinal Pigment Epithelial Cells
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The Role of Peripherin-2/ROM1 Complexes in Photoreceptor Outer Segment Disc Morphogenesis
Tylor R Lewis1, Muayyad R Al-Ubaidi2,3, Muna I Naash2,3
1Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA. tylor.lewis@duke.edu.
Advances in Experimental Medicine and Biology
|July 13, 2023
Summary
Peripherin-2 (PRPH2) protein mutations cause inherited retinal diseases. The D2 loop of PRPH2 is crucial for forming protein complexes that organize photoreceptor outer segment discs.
Area of Science:
- Cell Biology
- Genetics
- Ophthalmology
Background:
- Photoreceptor cells possess outer segments containing disc membranes essential for vision.
- Peripherin-2 (PRPH2), a tetraspanin protein in disc rims, is vital for outer segment structure.
- Mutations in the PRPH2 gene are linked to various inherited retinal degenerations.
Purpose of the Study:
- To investigate the supramolecular organization of peripherin-2/ROM1 complexes.
- To understand the role of the peripherin-2 D2 loop in protein interactions and oligomerization.
- To elucidate the contribution of these complexes to outer segment disc morphogenesis.
Main Methods:
- Analysis of peripherin-2 (PRPH2) gene mutations.
- Study of intermolecular interactions between peripherin-2 and ROM1.
- Investigation of the structural role of the D2 loop in peripherin-2 oligomerization.
Main Results:
- The D2 loop of peripherin-2 mediates interactions with itself and ROM1.
- These interactions result in the formation of large, ordered peripherin-2/ROM1 oligomers.
- The supramolecular organization of these complexes is critical for disc morphogenesis.
Conclusions:
- The D2 loop of peripherin-2 is a key functional domain for protein assembly.
- Peripherin-2/ROM1 complexes play a fundamental role in the structural integrity of photoreceptor discs.
- Understanding these interactions may offer insights into treating inherited retinal degenerations caused by PRPH2 mutations.
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