Pten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina.
Cell Rep
; 43(4): 114005, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38551961
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.
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Base de dados:
MEDLINE
Assunto principal:
Retina
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Adesão Celular
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Células Amácrinas
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Endocitose
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PTEN Fosfo-Hidrolase
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Via de Sinalização Wnt
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Canadá