Cell Reports (Apr 2024)
Pten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina
- Yacine Touahri,
- Joseph Hanna,
- Nobuhiko Tachibana,
- Satoshi Okawa,
- Hedy Liu,
- Luke Ajay David,
- Thomas Olender,
- Lakshmy Vasan,
- Alissa Pak,
- Dhruv Nimesh Mehta,
- Vorapin Chinchalongporn,
- Anjali Balakrishnan,
- Robert Cantrup,
- Rajiv Dixit,
- Pierre Mattar,
- Fermisk Saleh,
- Yaroslav Ilnytskyy,
- Monzur Murshed,
- Paul E. Mains,
- Igor Kovalchuk,
- Julie L. Lefebvre,
- Hon S. Leong,
- Michel Cayouette,
- Chao Wang,
- Antonio del Sol,
- Marjorie Brand,
- Benjamin E. Reese,
- Carol Schuurmans
Affiliations
- Yacine Touahri
- 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
- Joseph Hanna
- 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
- Nobuhiko Tachibana
- 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
- Satoshi Okawa
- 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
- Hedy Liu
- 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
- Luke Ajay David
- 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
- Thomas Olender
- Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada
- Lakshmy Vasan
- 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
- Alissa Pak
- 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
- Dhruv Nimesh Mehta
- 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
- Vorapin Chinchalongporn
- 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
- Anjali Balakrishnan
- 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
- Robert Cantrup
- Department of Biochemistry and Molecular Biology, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada
- Rajiv Dixit
- 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
- Pierre Mattar
- Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada
- Fermisk Saleh
- 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
- Yaroslav Ilnytskyy
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada
- Monzur Murshed
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3G 1A6, Canada
- Paul E. Mains
- Department of Biochemistry and Molecular Biology, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada
- Igor Kovalchuk
- Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada
- Julie L. Lefebvre
- 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
- Hon S. Leong
- 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
- Michel Cayouette
- Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada
- Chao Wang
- 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
- Antonio del Sol
- 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
- Marjorie Brand
- Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada
- Benjamin E. Reese
- Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106-5060, USA
- Carol Schuurmans
- 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; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 4
p. 114005
Abstract
Summary: 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.
