Pten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina
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Date
2024
Authors
Touahri, Yacine
Hanna, Joseph
Tachibana, Nobuhiko
Okawa, Satoshi
Liu, Hedy
David, Luke Ajay
Olender, Thomas
Vasan, Lakshmy
Pak, Alissa
Mehta, Dhruv Nimesh
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
The 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.
Description
Open access article. Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International license (CC BY-NC-ND 4.0) applies
Keywords
DSCAM , Cell adhesion molecules , Endocytic recycling , Retinal mosaics , Starburst amacrine cells , PTEN phosphatase , Extracellular vesicles , Wnt signaling
Citation
Touahri, 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