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

Autor:	Touahri Y; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada., Hanna J; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Tachibana N; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada., Okawa S; Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Liu H; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada., David LA; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Olender T; Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada., Vasan L; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Pak A; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Mehta DN; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada., Chinchalongporn V; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada., Balakrishnan A; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada., Cantrup R; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada., Dixit R; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada., Mattar P; Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada., Saleh F; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada., Ilnytskyy Y; Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada., Murshed M; Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3G 1A6, Canada., Mains PE; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada., Kovalchuk I; Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada., Lefebvre JL; Department of Molecular Genetics, University of Toronto, Toronto ON M5S 1A8, Canada; Program for Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Leong HS; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada., Cayouette M; Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada., Wang C; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Immunology, University of Toronto, Toronto, ON M5G 1L7, Canada., Del Sol A; Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; CIC bioGUNE, Bizkaia Technology Park, 48160 Derio, Spain; IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain., Brand M; Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada., Reese BE; Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106-5060, USA., Schuurmans C; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: cschuurm@sri.utoronto.ca.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Apr 23; Vol. 43 (4), pp. 114005. Date of Electronic Publication: 2024 Mar 27.
DOI:	10.1016/j.celrep.2024.114005
Abstrakt:	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 (Pten cKO ) retinas. Wnt signaling molecules are also enriched in Pten cKO 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. Competing Interests: Declaration of interests The authors declare no competing interests (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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