Usher syndrome type 1-associated cadherins shape the photoreceptor outer segment

Area of Science:

• Ophthalmology
• Genetics
• Cell Biology

Background:

• Usher syndrome type 1 (USH1) causes combined hearing and vision loss.
• The underlying mechanisms of USH1-related retinal dystrophy are not fully understood.
• USH1 proteins are linked to calyceal processes, microvilli near photoreceptor outer segments.

Purpose of the Study:

• Investigate the function of USH1 proteins, specifically protocadherin-15 (USH1F), in photoreceptor structure and function.
• Determine the role of calyceal processes and their associated links in retinal development.
• Elucidate the molecular basis of retinal dystrophy in USH1.

Main Methods:

• Utilized *Xenopus tropicalis* as a model organism.
• Employed a knockdown approach to reduce protocadherin-15 (USH1F) and cadherin-23 (USH1D) levels.
• Examined photoreceptor morphology, function, and F-actin content using microscopy.

Main Results:

• Protocadherin-15 deficiency disrupted photoreceptor outer segment structure and function.
• Abnormalities included excessive rod basal outer disk outgrowth and curved cone outer segments.
• Calyceal processes were reduced in cones and showed decreased F-actin in rods, indicating impaired development/maintenance.

Conclusions:

• Protocadherin-15-containing links are essential for calyceal process development and maintenance.
• Calyceal processes and their links regulate photoreceptor outer segment disk and lamellae sizing.
• This provides a novel mechanism linking USH1 gene mutations to retinal dystrophy.