BBSome-Mediated Clearance of Ubiquitinated IMPG2 Defines a Constitutive Ciliary Retrieval Pathway in Photoreceptors.

ABSTRACT: The BBSome mediates the retrieval of ubiquitinated membrane proteins from cilia, but its physiological cargoes in photoreceptors remain largely unidentified. Here, we find that K63-linked ubiquitin (UbK63) chains accumulate in the outer segment (OS, equivalent of cilia) of Bbs4 ^-/- photoreceptors from the onset of OS formation. Through quantitative profiling of the UbK63-associated OS proteome, we identify the transmembrane fragment of interphotoreceptor matrix proteoglycan 2 (IMPG2^m) as a principal cargo of the BBSome. In Bbs4 ^-/- mice, ubiquitinated IMPG2^m aberrantly accumulates in OSs, and disruption of IMPG2^m ubiquitination impairs its retrieval and clearance. Because full-length IMPG2 traffics to the OS to deliver it

SUBMITTER: Das T 

PROVIDER: S-EPMC12324355 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature