title: An unconventional secretory pathway mediates the cilia targeting of peripherin/rds.
abstract: It is unclear how unconventional secretion interplays with conventional secretion for the normal maintenance and renewal of membrane structures. The photoreceptor sensory cilium is recognized for fast membrane renewal, for which rhodopsin and peripherin/rds (P/rds) play critical roles. Here, we provide evidence that P/rds is targeted to the cilia by an unconventional secretion pathway. When expressed in ciliated hTERT-RPE1 human cell line, P/rd is localized to cilia. Cilium trafficking of P/rds was sustained even when the Golgi functions, including trans-Golgi-mediated conventional secretion, were inhibited by the small molecules brefeldin A, 30N12, and monensin. The unconventional cilia targeting of P/rds is dependent on COPII-mediated exit from the ER, but appears to be independent of GRASP55-mediated secretion. The regions in the C-terminal tail of P/rds are essential for this unconventional trafficking. In the absence of the region required for cilia targeting, P/rds was prohibited from entering the secretory pathways and was retained in the Golgi apparatus. A region essential for this Golgi retention was also found in the C-terminal tail of P/rds and supported the cilia targeting of P/rds mediated by unconventional secretion. In ciliated cells, including bovine and Xenopus laevis rod photoreceptors, P/rds was robustly sensitive to endoglycosidase H, which is consistent with its bypassing the medial Golgi and traversing the unconventional secretory pathway. Because rhodopsin is known to traffic through conventional secretion, this study of P/rds suggests that both conventional secretion and unconventional secretion need to cooperate for the renewal of the photoreceptor sensory cilium.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4965.
authors.forename: Guilian
authors.initials: G
authors.lastname: Tian
authors.forename: Philip
authors.initials: P
authors.lastname: Ropelewski
authors.forename: Ina
authors.initials: I
authors.lastname: Nemet
authors.forename: Richard
authors.initials: R
authors.lastname: Lee
authors.forename: Kerrie H
authors.initials: KH
authors.lastname: Lodowski
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Imanishi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002417:Cattle; D002460:Cell Line; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D064531:Peripherins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D055571:Secretory Pathway / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D064531:Peripherins
keywords: cilia; peripherin/rds; photoreceptor; retina; trafficking; unconventional secretion