PXD038015-1

PXD038015 is an original dataset announced via ProteomeXchange.

Title	Ciliary tip actin dynamics regulate the cadence of photoreceptor disc formation
Description	As signalling organelles, primary cilia regulate their membrane G protein-coupled receptor (GPCR) content by ectocytosis, a process requiring localised actin dynamics at their tip to alter membrane shape.1,2 Mammalian photoreceptor outer segments comprise an expanse of folded membranes (discs) at the tip of highly-specialised connecting cilia (CC), in which photosensitive GPCRs like rhodopsin are concentrated. In an extraordinary feat of biology, outer segment discs are shed and remade daily.3 Defects in this process, due to genetic mutations, cause retinitis pigmentosa (RP), an untreatable, blinding disease. The mechanism by which photoreceptor cilia generate outer segments is therefore fundamental for vision yet poorly understood. Here, we show the membrane deformation required for outer segment disc genesis is driven by dynamic changes in the actin cytoskeleton in a process akin to ectocytosis. Further, we show RPGR, a leading causal RP gene, regulates activity of actin binding proteins crucial to this process. Disc genesis is compromised in Rpgr mouse models, slowing the actin dynamics required for timely disc formation, leading to aborted membrane shedding as ectosome-like vesicles, photoreceptor death and visual loss. Manipulation of actin dynamics partially rescues the phenotype, suggesting this pathway could be targeted therapeutically. These findings help define how actin-mediated dynamics control outer segment turnover.
HostingRepository	PRIDE
AnnounceDate	2024-05-08
AnnouncementXML	Submission_2024-05-08_01:50:57.610.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von kriegsheim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-07 10:07:44	ID requested
⏵ 1	2024-05-08 01:50:57	announced
2	2024-10-22 06:38:33	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: LC-MS,cilia, retina

a von kiregshiem
contact affiliation	university of edinburgh
contact email	avonkri@ed.ac.uk
lab head
Alex von kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@ucd.ie
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD038015

PRIDE project URI

• PRIDE
  1. PXD038015
     1. Label: PRIDE project
     2. Name: Ciliary tip actin dynamics regulate the cadence of photoreceptor disc formation