Pten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina

Simple item page
dc.contributor.authorTouahri, Yacine
dc.contributor.authorHanna, Joseph
dc.contributor.authorTachibana, Nobuhiko
dc.contributor.authorOkawa, Satoshi
dc.contributor.authorLiu, Hedy
dc.contributor.authorDavid, Luke Ajay
dc.contributor.authorOlender, Thomas
dc.contributor.authorVasan, Lakshmy
dc.contributor.authorPak, Alissa
dc.contributor.authorMehta, Dhruv Nimesh
dc.contributor.authorChinchalongporn, Vorapin
dc.contributor.authorBalakrishnan, Anjali
dc.contributor.authorCantrup, Robert
dc.contributor.authorDixit, Rajiv
dc.contributor.authorMattar, Pierre
dc.contributor.authorSaleh, Fermisk
dc.contributor.authorIlnytskyy, Yaroslav
dc.contributor.authorMurshed, Monzur
dc.contributor.authorMains, Paul E.
dc.contributor.authorKovalchuk, Igor
dc.contributor.authorLefebvre, Julie L.
dc.contributor.authorLeong, Hon S.
dc.contributor.authorCayouette, Michel
dc.contributor.authorWang, Chao
dc.contributor.authordel Sol, Antonio
dc.contributor.authorBrand, Marjorie
dc.contributor.authorReese, Benjamin E.
dc.contributor.authorSchuurmans, Carol
dc.date.accessioned2025-09-12T22:54:26Z
dc.date.available2025-09-12T22:54:26Z
dc.date.issued2024
dc.descriptionOpen access article. Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International license (CC BY-NC-ND 4.0) applies
dc.description.abstractThe retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam) are co-expressed and function additively to pattern starburst amacrine cell mosaics. Mechanistically, Pten loss accelerates the endocytic trafficking of DSCAM, FAT3, and MEGF10 off the cell membrane and into endocytic vesicles in amacrine cells. Accordingly, the vesicular proteome, a molecular signature of the cell of origin, is enriched in exocytosis, vesicle-mediated transport, and receptor internalization proteins in Pten conditional knockout (PtencKO) retinas. Wnt signaling molecules are also enriched in PtencKO retinal vesicles, and the genetic or pharmacological disruption of Wnt signaling phenocopies amacrine cell patterning defects. Pten thus controls vesicular trafficking of cell adhesion and signaling molecules to establish retinal amacrine cell mosaics.
dc.description.peer-reviewYes
dc.identifier.citationTouahri, Y., Hanna, J., Tachibana, N., Okawa, S., Liu, H., David, L. A., Olender, T., Vasan, L., Pak, A., Mehta, D. N., Chinchalongporn, V., Balakrishnan, A., Cantrup, R., Dixit, R., Mattar, P., Saleh, F., Ilnytskyy, Y., Murshed, M., Mains, P. E.,...Schuurmans, C. (2024. Pten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina. Cell Reports, 43(4), Article 114005. https://doi.org/10.1016/j.celrep.2024.114005
dc.identifier.urihttps://hdl.handle.net/10133/7129
dc.language.isoen
dc.publisherElsevier
dc.publisher.departmentDepartment of Biological Sciences
dc.publisher.facultyArts and Science
dc.publisher.institutionSunnybrook Research Institute
dc.publisher.institutionUniversity of Toronto
dc.publisher.institutionUniversity of Calgary
dc.publisher.institutionUniversity of Luxembourg
dc.publisher.institutionUniversity of Pittsburgh School of Medicine
dc.publisher.institutionUniversity of Ottawa
dc.publisher.institutionInstitut de Recherches Cliniques de Montréal
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.institutionMcGill University
dc.publisher.institutionHospital for Sick Children, Toronto
dc.publisher.institutionBizkaia Technology Park
dc.publisher.institutionBasque Foundation for Science
dc.publisher.institutionUniversity of California
dc.publisher.urlhttps://doi.org/10.1016/j.celrep.2024.114005
dc.subjectDSCAM
dc.subjectCell adhesion molecules
dc.subjectEndocytic recycling
dc.subjectRetinal mosaics
dc.subjectStarburst amacrine cells
dc.subjectPTEN phosphatase
dc.subjectExtracellular vesicles
dc.subjectWnt signaling
dc.titlePten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina
dc.typeArticle
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Kovalchuk,I-Pten-regulates.pdf
Size:
11.2 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.75 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Kovalchuk, Igor