Open AccessTmem138 is localized to the connecting cilium essential for rhodopsin localization and outer segment biogenesis
Author(s) -
Dianlei Guo,
Jiali Ru,
Lijing Xie,
Mingjuan Wu,
Yingchun Su,
ShiYong Zhu,
Shujuan Xu,
Bin Zou,
Yanhong Wei,
Xialin Liu,
Yizhi Liu,
Chunqiao Liu
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109934119
Subject(s) - ciliopathies , cilium , biology , ciliogenesis , microbiology and biotechnology , rhodopsin , basal body , retinal degeneration , transmembrane protein , mutant , biogenesis , germline , retinal , genetics , gene , phenotype , flagellum , receptor , biochemistry
Significance The connecting cilium (CC) of the photoreceptor provides the only route for the trafficking of the outer segment (OS) proteins. Failure of OS protein transport causes degenerative photoreceptor diseases, including retinitis pigmentosa. We demonstrate that Tmem138, a protein linked to ciliopathy, is localized to the photoreceptor CC. Germline deletion of Tmem138 abolished OS morphogenesis, followed by rapid photoreceptor degeneration. Tmem138 interacts with rhodopsin and two additional CC compartment proteins, Ahi1 and Tmem231, likely forming a membrane complex to facilitate trafficking of rhodopsin and other OS-bound proteins across the CC. The study thus implicates a new line of regulation on the delivery of OS proteins through interactions with CC membrane complex(es) and provides insights into photoreceptor ciliopathy diseases.