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

TitleSPATA7 maintains a novel photoreceptor-specific zone in the distal connecting cilium.
Publication TypeJournal Article
Year of Publication2018
AuthorsDharmat, R, Eblimit, A, Robichaux, MA, Zhang, Z, Nguyen, T-MT, Jung, SYun, He, F, Jain, A, Li, Y, Qin, J, Overbeek, P, Roepman, R, Mardon, G, Wensel, TG, Chen, R
JournalJ Cell Biol
Volume217
Issue8
Pagination2851-2865
Date Published2018 Aug 06
ISSN1540-8140
KeywordsAdaptor Proteins, Signal Transducing, Animals, Antigens, Neoplasm, Carrier Proteins, Cell Cycle Proteins, Cytoskeletal Proteins, DNA-Binding Proteins, Eye Proteins, Mice, Mice, Inbred C57BL, Nuclear Proteins, Photoreceptor Connecting Cilium, Protein Transport
Abstract

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.

DOI10.1083/jcb.201712117
Alternate JournalJ Cell Biol
PubMed ID29899041
PubMed Central IDPMC6080925
Grant ListF32 EY027171 / EY / NEI NIH HHS / United States
R01 EY020540 / EY / NEI NIH HHS / United States
R01 EY011900 / EY / NEI NIH HHS / United States
R01 EY026545 / EY / NEI NIH HHS / United States
R01 EY022356 / EY / NEI NIH HHS / United States
P30 EY002520 / EY / NEI NIH HHS / United States
R01 EY018571 / EY / NEI NIH HHS / United States
R01 EY007981 / EY / NEI NIH HHS / United States
R01 EY025218 / EY / NEI NIH HHS / United States

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