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Prph2 initiates outer segment morphogenesis but maturation requires Prph2/Rom1 oligomerization.

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The peripherin 2 (PRPH2) C-terminus initiates photoreceptor outer segment (OS) formation, while its full structure and ROM1 are needed for OS maturation. ROM1 regulates PRPH2 trafficking and OS development.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Retinal Research

Background:

  • Peripherin 2 (PRPH2) is crucial for photoreceptor outer segment (OS) formation.
  • PRPH2 functions in oligomers with its homolog ROM1, but their precise roles in OS morphogenesis are unclear.

Purpose of the Study:

  • To elucidate the specific roles of PRPH2 and ROM1 in OS morphogenesis.
  • To investigate how ROM1 influences PRPH2 trafficking and OS development.

Main Methods:

  • Generated a knock-in mouse model expressing a chimeric protein (RRCT) of Rom1 and Prph2.
  • Assessed OS initiation and maturation in RRCT mice, with and without Rom1.
  • Evaluated PRPH2 trafficking pathways using the RRCT model.

Main Results:

  • The Prph2 C-terminus alone is sufficient for OS initiation.
  • OS maturation requires the full Prph2 protein body and associated oligomers.
  • Removing Rom1 rescues defects in RRCT heterozygous rods, indicating Rom1's regulatory role.
  • Rom1 dictates PRPH2 complex trafficking via conventional or unconventional secretory pathways.

Conclusions:

  • The Prph2 C-terminus is essential for initiating OS formation.
  • ROM1 acts as a critical regulator of PRPH2 trafficking and OS morphogenesis.
  • These findings clarify the molecular mechanisms underlying OS development and PRPH2-ROM1 interactions.