Phosphatidylserine Externalization Results from and Causes Neurite Degeneration in Drosophila

Cell Reports
Maria L SaparChun Han

Abstract

Phagocytic clearance of degenerating dendrites or axons is critical for maintaining tissue homeostasis and preventing neuroinflammation. Externalized phosphatidylserine (PS) has been postulated to be an "eat-me" signal allowing recognition of degenerating neurites by phagocytes. Here we show that in Drosophila, PS is dynamically exposed on degenerating dendrites during developmental pruning and after physical injury, but PS exposure is suppressed when dendrite degeneration is genetically blocked. Ectopic PS exposure via phospholipid flippase knockout and scramblase overexpression induced PS exposure preferentially at distal dendrites and caused distinct modes of neurite loss that differ in larval sensory dendrites and in adult olfactory axons. Surprisingly, extracellular lactadherin that lacks the integrin-interaction domain induced phagocyte-dependent degeneration of PS-exposing dendrites, revealing an unidentified bridging function that potentiates phagocytes. Our findings establish a direct causal relationship between PS exposure and neurite degeneration in vivo.

Citations

Jul 3, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wen LiuLifen Gao
May 16, 2020·Critical Reviews in Biochemistry and Molecular Biology·Hye-Won Shin, Hiroyuki Takatsu
Jun 13, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Chieh Chang, Naoki Hisamoto
Jul 14, 2020·The EMBO Journal·Nicole Scott-HewittMichela Matteoli
Jan 22, 2021·Neuroscience Research·Masahiro Maruoka, Jun Suzuki
May 5, 2020·Biophysical Journal·Mason L ValentineCarlos R Baiz
Apr 18, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Angélica María Sabogal-GuáquetaGloria Patricia Cardona-Gómez
Feb 21, 2021·Journal of Neurochemistry·Claire A ButlerGuy C Brown
Mar 31, 2021·Proceedings of the National Academy of Sciences of the United States of America·Gabriel T KoremanChun Han
May 21, 2021·The EMBO Journal·Jungjoo ParkWon-Suk Chung
Jun 18, 2021·Frontiers in Cellular Neuroscience·Chang YinJay Z Parrish
Aug 27, 2021·Membranes·Miliça RistovskiJyh-Yeuan Lee
Sep 3, 2021·Neural Regeneration Research·Jessica CornellMiou Zhou
Nov 16, 2021·ELife·Kwang Woo KoAaron DiAntonio

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