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Glutathione S-transferase Pi (Gstp) proteins regulate neuritogenesis in the developing cerebral cortex
Journal article   Open access   Peer reviewed

Glutathione S-transferase Pi (Gstp) proteins regulate neuritogenesis in the developing cerebral cortex

Xiaonan Liu, Sara M Blazejewski, Sarah A Bennison and Kazuhito Toyo-Oka
Human molecular genetics, v 30(1), pp 30-45
25 Mar 2021
PMID: 33437989
url
https://doi.org/10.1093/hmg/ddab003View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Animals Cerebral Cortex - growth & development Cerebral Cortex - metabolism Dendrites - genetics Dendrites - pathology Embryonic Development - genetics Gene Expression Regulation, Developmental - genetics Glutathione - genetics Glutathione S-Transferase pi - genetics Humans MAP Kinase Signaling System - genetics Mice Neurites - metabolism Neurites - pathology Neurogenesis - genetics Oxidative Stress - genetics Pyramidal Cells - metabolism Pyramidal Cells - pathology
GSTP proteins are metabolic enzymes involved in the removal of oxidative stress and intracellular signaling and also have inhibitory effects on JNK activity. However, the functions of Gstp proteins in the developing brain are unknown. In mice, there are three Gstp proteins, Gstp1, 2 and 3, whereas there is only one GSTP in humans. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, we found that Gstp1 was expressed beginning at E15.5 in the cortex, but Gstp2 and 3 started expressing at E18.5. Gstp 1 and 2 knockdown (KD) caused decreased neurite number in cortical neurons, implicating them in neurite initiation. Using in utero electroporation (IUE) to knock down Gstp1 and 2 in layer 2/3 pyramidal neurons in vivo, we found abnormal swelling of the apical dendrite at P3 and reduced neurite number at P15. Using time-lapse live imaging, we found that the apical dendrite orientation was skewed compared with the control. We explored the molecular mechanism and found that JNK inhibition rescued reduced neurite number caused by Gstp knockdown, indicating that Gstp regulates neurite formation through JNK signaling. Thus, we found novel functions of Gstp proteins in neurite initiation during cortical development. These findings not only provide novel functions of Gstp proteins in neuritogenesis during cortical development but also help us to understand the complexity of neurite formation.

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Web of Science research areas
Biochemistry & Molecular Biology
Genetics & Heredity
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