Pten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina.
Journal: Cell reports
Volume: 43
Issue: 4
Year of Publication:
Affiliated Institutions:
Biological Sciences Platform, Sunnybrook Research Institute, Bayview Avenue, Toronto, ON MN M, Canada; Department of Biochemistry, University of Toronto, Toronto, ON MS A, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON MT A, Canada.
Biological Sciences Platform, Sunnybrook Research Institute, Bayview Avenue, Toronto, ON MN M, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON MT A, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON MS A, Canada.
Biological Sciences Platform, Sunnybrook Research Institute, Bayview Avenue, Toronto, ON MN M, Canada; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB TN N, Canada.
Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 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.
Biological Sciences Platform, Sunnybrook Research Institute, Bayview Avenue, Toronto, ON MN M, Canada; Department of Biochemistry, University of Toronto, Toronto, ON MS A, Canada.
Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON KH L, Canada.
Biological Sciences Platform, Sunnybrook Research Institute, Bayview Avenue, Toronto, ON MN M, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON MS A, Canada.
Biological Sciences Platform, Sunnybrook Research Institute, Bayview Avenue, Toronto, ON MN M, Canada; Department of Biochemistry, University of Toronto, Toronto, ON MS A, Canada; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB TN N, Canada.
Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB TN N, Canada.
Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC HW R, Canada.
Department of Biological Sciences, University of Lethbridge, Lethbridge, AB TK M, Canada.
Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC HG A, Canada.
Department of Molecular Genetics, University of Toronto, Toronto ON MS A, Canada; Program for Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON MG A, Canada.
Biological Sciences Platform, Sunnybrook Research Institute, Bayview Avenue, Toronto, ON MN M, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON MG L, Canada.
Biological Sciences Platform, Sunnybrook Research Institute, Bayview Avenue, Toronto, ON MN M, Canada; Department of Immunology, University of Toronto, Toronto, ON MG L, Canada.
Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg; CIC bioGUNE, Bizkaia Technology Park, Derio, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA -, USA.
Biological Sciences Platform, Sunnybrook Research Institute, Bayview Avenue, Toronto, ON MN M, Canada; Department of Biochemistry, University of Toronto, Toronto, ON MS A, Canada; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON MT A, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON MS A, Canada; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB TN N, Canada. Electronic address: cschuurm@sri.utoronto.ca.
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 moleculeDscam) 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) retinas. Wnt signaling molecules are also enriched in Pten 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.
Authors & Co-authors:
Touahri
Hanna
Tachibana
Okawa
Liu
David
Olender
Vasan
Pak
Mehta
Chinchalongporn
Balakrishnan
Cantrup
Dixit
Mattar
Saleh
Ilnytskyy
Murshed
Mains
Kovalchuk
Lefebvre
Leong
Cayouette
Wang
Sol
Brand
Reese
Schuurmans
Study Outcome
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