PUBLICATION
Cdhr1a and pcdh15b may link photoreceptor outer segments with calyceal processes revealing a potential mechanism for cone-rod dystrophy
- Authors
- Patel, M.K., Piedade, W.P., Famulski, J.K.
- ID
- ZDB-PUB-260418-1
- Date
- 2026
- Source
- eLIFE 13: (Journal)
- Registered Authors
- Famulski, Jakub, Patel, Meet
- Keywords
- calyceal process, cdhr1, cone-rod dystrophy, developmental biology, pcdh15, zebrafish
- MeSH Terms
- none
- PubMed
- 41995082 Full text @ Elife
Citation
Patel, M.K., Piedade, W.P., Famulski, J.K. (2026) Cdhr1a and pcdh15b may link photoreceptor outer segments with calyceal processes revealing a potential mechanism for cone-rod dystrophy. eLIFE. 13:.
Abstract
Cone-rod dystrophy (CRD) is a macular degeneration disorder characterized by initial cone cell degeneration. Mutations in CDHR1, a photoreceptor-specific cadherin, have been found to be associated with the incidence of CRD. While studying the function of CDHR1, we observed that the localization of the zebrafish homologue, cdhr1a, resembles that of calyceal process (CPs). When co-labeling CPs using pcdh15b, we observed that cdhr1a, in the outer segment (OS), juxtaposes with pcdh15b, found in the CP. Similar localization patterns were detected in human, macaque, xenopus, ducks, gerbil, and mouse. Using immunoprecipitation and K652 cell aggregation assays, we demonstrate that pcdh15b and cdhr1a can interact and thus potentially link the OS and CP. To analyze the consequences of OS-CP interactions in CRD, we established a cdhr1a mutant line (cdhr1afs*146). Homozygous cdhr1afs*146 mutants exhibit minor cone OS defects starting at 15 dpf and severe OS disruption and cell loss by 3 months. Shortening of CPs coincided with cone OS defects which were significantly exacerbated when combined with the loss of pcdh15b. Rod OS defects were mild and delayed until 3-6 months. In conclusion, we propose that cdhr1a and pcdh15b function to link cone OSs with CPs and maintain OS integrity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping