SPATA7 maintains a novel photoreceptor-specific zone in the distal connecting cilium

Photoreceptor-specific ciliopathies often affect a structure that is considered functionally homologous to the ciliary transition zone (TZ) called the connecting cilium (CC). However, it is unclear how mutations in certain ciliary genes disrupt the photoreceptor CC without impacting the primary cili...

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Bibliographic Details
Published in:The Journal of cell biology 2018-08, Vol.217 (8), p.2851-2865
Main Authors: Dharmat, Rachayata, Eblimit, Aiden, Robichaux, Michael A, Zhang, Zhixian, Nguyen, Thanh-Minh T, Jung, Sung Yun, He, Feng, Jain, Antrix, Li, Yumei, Qin, Jun, Overbeek, Paul, Roepman, Ronald, Mardon, Graeme, Wensel, Theodore G, Chen, Rui
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - analysis
Adaptor Proteins, Signal Transducing - metabolism
Animals
Antigens, Neoplasm
Carrier Proteins - analysis
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Cycle Proteins
Cilia
Cytoskeletal Proteins
Degeneration
Destabilization
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - physiology
Eye Proteins - analysis
Eye Proteins - genetics
Eye Proteins - metabolism
Genotype & phenotype
Homology
Mice
Mice, Inbred C57BL
Microscopy
Microtubules
Mutation
Nuclear Proteins - metabolism
Nuclear Proteins - physiology
Phenotypes
Photoreceptor Connecting Cilium - metabolism
Photoreceptor Connecting Cilium - ultrastructure
Photoreceptors
Protein Transport - genetics
Proteins
Retinal degeneration
Stochasticity
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Summary:Photoreceptor-specific ciliopathies often affect a structure that is considered functionally homologous to the ciliary transition zone (TZ) called the connecting cilium (CC). However, it is unclear how mutations in certain ciliary genes disrupt the photoreceptor CC without impacting the primary cilia systemically. By applying stochastic optical reconstruction microscopy technology in different genetic models, we show that the CC can be partitioned into two regions: the proximal CC (PCC), which is homologous to the TZ of primary cilia, and the distal CC (DCC), a photoreceptor-specific extension of the ciliary TZ. This specialized distal zone of the CC in photoreceptors is maintained by SPATA7, which interacts with other photoreceptor-specific ciliary proteins such as RPGR and RPGRIP1. The absence of results in the mislocalization of DCC proteins without affecting the PCC protein complexes. This collapse results in destabilization of the axonemal microtubules, which consequently results in photoreceptor degeneration. These data provide a novel mechanism to explain how genetic disruption of ubiquitously present ciliary proteins exerts tissue-specific ciliopathy phenotypes.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201712117