Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Maemoto Y

PROVIDER: S-EPMC7396612 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

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

Maemoto Yuki Y Maruyama Tomohiro T Nemoto Kazuaki K Baba Takashi T Motohashi Manae M Ito Akihiro A Tagaya Mitsuo M Tani Katsuko K

Frontiers in cell and developmental biology 20200723

DDHD1 and DDHD2 are both intracellular phospholipases A<sub>1</sub> and hydrolyze phosphatidic acid <i>in vitro</i>. 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. ...[more]

PMID: 32850804

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Project description:Cell-based assays covering environmentally relevant modes of action are widely used for water quality monitoring. However, no high-throughput assays are available for testing developmental neurotoxicity of water samples. We implemented an assay that quantifies neurite outgrowth, which is one of the neurodevelopmental key events, and cell viability in human neuroblastoma SH-SY5Y cells using imaging techniques. We used this assay for testing of extracts of surface water collected in agricultural areas during rain events and effluents from wastewater treatment plants (WWTPs), where more than 200 chemicals had been quantified. Forty-one chemicals were tested individually that were suspected to contribute to the mixture effects among the detected chemicals in environmental samples. Sample sensitivity distributions indicated higher neurotoxicity for surface water samples than for effluents, and the endpoint of neurite outgrowth inhibition was six times more sensitive than cytotoxicity in the surface water samples and only three times more sensitive in the effluent samples. Eight environmental pollutants showed high specificity, and those ranged from pharmaceuticals (mebendazole and verapamil) to pesticides (methiocarb and clomazone), biocides (1,2-benzisothiazolin-3-one), and industrial chemicals (N-methyl-2-pyrrolidone, 7-diethylamino-4-methylcoumarin, and 2-(4-morpholinyl)benzothiazole). Although neurotoxic effects were newly detected for some of our test chemicals, less than 1% of the measured effects were explained by the detected and toxicologically characterized chemicals. The neurotoxicity assay was benchmarked against other bioassays: activations of the aryl hydrocarbon receptor and the peroxisome proliferator-activated receptor were similar in sensitivity, highly sensitive and did not differ much between the two water types, with surface water having slightly higher effects than the WWTP effluent. Oxidative stress response mirrored neurotoxicity quite well but was caused by different chemicals in the two water types. Overall, the new cell-based neurotoxicity assay is a valuable complement to the existing battery of effect-based monitoring tools.

Dataset Information

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

Publications

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

Similar Datasets

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