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...
Main Authors: | , , , , , , , |
---|---|
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 |
_version_ | 1819182304888619008 |
---|---|
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. |
first_indexed | 2024-12-22T22:44:01Z |
format | Article |
id | doaj.art-59ff45338bbc44e59edf7cb8a11cf37e |
institution | Directory Open Access Journal |
issn | 2296-634X |
language | English |
last_indexed | 2024-12-22T22:44:01Z |
publishDate | 2020-07-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Cell and Developmental Biology |
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 |
work_keys_str_mv | AT yukimaemoto ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes AT tomohiromaruyama ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes AT kazuakinemoto ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes AT takashibaba ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes AT takashibaba ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes AT manaemotohashi ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes AT akihiroito ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes AT mitsuotagaya ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes AT katsukotani ddhd1butnotddhd2suppressesneuriteoutgrowthinshsy5yandpc12cellsbyregulatingproteintransportfromrecyclingendosomes |