Spata7 Is Required for Maintenance of the Retinal Connecting Cilium

Authors

Jiaxiong Lu
Kaitlyn Xiong
Xinye Qian
Jongsu Choi
Yoon-Kyung Shim
Jacob Burnett
Graeme Mardon
Rui Chen

Publication Date

4-2-2022

Journal

Scientific Reports

DOI

10.1038/s41598-022-09530-0

PMID

35368022

PMCID

PMC8976851

PubMedCentral® Posted Date

4-2-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Cilia, DNA-Binding Proteins, Electroretinography, Mice, Retina, Retinal Degeneration, Rhodopsin, Neurodegeneration, Cell death, Stress signalling

Abstract

SPATA7, an early onset LCA3 retinal disease gene, encodes a putative scaffold protein that is essential for the proper assembly of the connecting cilium (CC) complex in photoreceptors. Previous studies have shown that SPATA7 interacts with other photoreceptor-specific ciliary proteins, such as RPGR and RPGRIP1, and maintains the integrity of CC integrity. However, although it is known that Spata7 is required for early formation of the CC, it is unclear if Spata7 is also required for the maintenance of the CC. To investigate Spata7 function in the retina at the adult stage, loss of function was induced in the adult retina upon tamoxifen induction of an inducible Spata7 knockout allele (Spata7flox/−; UbcCreERT2/+). The phenotype of mutant retina was characterized by a combination of histology, immunobiochemistry, and electroretinography (ERG). Our results demonstrated that Spata7 is also essential for maintaining the integrity of the mature retinal CC. Loss of Spata7 in adults caused phenotypes similar to those seen in germline mutant mice, including photoreceptor cell degeneration and defective ERG responses. Close examination of the CC revealed significantly shortened NPHP1 length as a result of Spata7 deletion. Furthermore, mislocalization of rhodopsin, leading to ER stress-mediated apoptosis, was observed in the retinal layers. Our results indicate that Spata7 is required not only for the establishment but also for the maintenance of the CC of photoreceptors.

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