DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes

DDHD1 and DDHD2 are both intracellular phospholipases A1 and hydrolyze phosphatidic acid in vitro. Given that phosphatidic acid participates in neurite outgrowth, we examined whether DDHD1 and DDHD2 regulate neurite outgrowth. Depletion of DDHD1 from SH-SY5Y and PC12 cells caused elongation of neuri...

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Main Authors: Yuki Maemoto, Tomohiro Maruyama, Kazuaki Nemoto, Takashi Baba, Manae Motohashi, Akihiro Ito, Mitsuo Tagaya, Katsuko Tani
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-07-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcell.2020.00670/full
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author Yuki Maemoto
Tomohiro Maruyama
Kazuaki Nemoto
Takashi Baba
Takashi Baba
Manae Motohashi
Akihiro Ito
Mitsuo Tagaya
Katsuko Tani
author_facet Yuki Maemoto
Tomohiro Maruyama
Kazuaki Nemoto
Takashi Baba
Takashi Baba
Manae Motohashi
Akihiro Ito
Mitsuo Tagaya
Katsuko Tani
author_sort Yuki Maemoto
collection DOAJ
description DDHD1 and DDHD2 are both intracellular phospholipases A1 and hydrolyze phosphatidic acid in vitro. Given that phosphatidic acid participates in neurite outgrowth, we examined whether DDHD1 and DDHD2 regulate neurite outgrowth. Depletion of DDHD1 from SH-SY5Y and PC12 cells caused elongation of neurites, whereas DDHD2 depletion prevented neurite elongation. Rescue experiments demonstrated that the enzymatic activity of DDHD1 is necessary for the prevention of neurite elongation. Depletion of DDHD1 caused enlargement of early endosomes and stimulated tubulation of recycling endosomes positive for phosphatidic acid-binding proteins syndapin2 and MICAL-L1. Knockout of DDHD1 enhanced transferrin recycling from recycling endosomes to the cell surface. Our results suggest that DDHD1 negatively controls the formation of a local phosphatidic acid-rich domain in recycling endosomes that serves as a membrane source for neurite outgrowth.
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spelling doaj.art-59ff45338bbc44e59edf7cb8a11cf37e2022-12-21T18:10:07ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-07-01810.3389/fcell.2020.00670556036DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling EndosomesYuki Maemoto0Tomohiro Maruyama1Kazuaki Nemoto2Takashi Baba3Takashi Baba4Manae Motohashi5Akihiro Ito6Mitsuo Tagaya7Katsuko Tani8School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, JapanSchool of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, JapanSchool of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, JapanSchool of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, JapanDepartment of Biological Informatics and Experimental Therapeutics, Graduate School of Medicine and Faculty of Medicine, Akita University, Akita, JapanSchool of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, JapanSchool of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, JapanSchool of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, JapanSchool of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, JapanDDHD1 and DDHD2 are both intracellular phospholipases A1 and hydrolyze phosphatidic acid in vitro. Given that phosphatidic acid participates in neurite outgrowth, we examined whether DDHD1 and DDHD2 regulate neurite outgrowth. Depletion of DDHD1 from SH-SY5Y and PC12 cells caused elongation of neurites, whereas DDHD2 depletion prevented neurite elongation. Rescue experiments demonstrated that the enzymatic activity of DDHD1 is necessary for the prevention of neurite elongation. Depletion of DDHD1 caused enlargement of early endosomes and stimulated tubulation of recycling endosomes positive for phosphatidic acid-binding proteins syndapin2 and MICAL-L1. Knockout of DDHD1 enhanced transferrin recycling from recycling endosomes to the cell surface. Our results suggest that DDHD1 negatively controls the formation of a local phosphatidic acid-rich domain in recycling endosomes that serves as a membrane source for neurite outgrowth.https://www.frontiersin.org/article/10.3389/fcell.2020.00670/fullendosomephospholipaseneuritephosphatidic acidrecycling
spellingShingle Yuki Maemoto
Tomohiro Maruyama
Kazuaki Nemoto
Takashi Baba
Takashi Baba
Manae Motohashi
Akihiro Ito
Mitsuo Tagaya
Katsuko Tani
DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes
Frontiers in Cell and Developmental Biology
endosome
phospholipase
neurite
phosphatidic acid
recycling
title DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes
title_full DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes
title_fullStr DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes
title_full_unstemmed DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes
title_short DDHD1, but Not DDHD2, Suppresses Neurite Outgrowth in SH-SY5Y and PC12 Cells by Regulating Protein Transport From Recycling Endosomes
title_sort ddhd1 but not ddhd2 suppresses neurite outgrowth in sh sy5y and pc12 cells by regulating protein transport from recycling endosomes
topic endosome
phospholipase
neurite
phosphatidic acid
recycling
url https://www.frontiersin.org/article/10.3389/fcell.2020.00670/full
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AT katsukotani ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes