Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development
Huntington-interacting protein 1-related protein (HIP1R) was identified on the basis of its structural homology with HIP1. Based on its domain structure, HIP1R is a putative endocytosis-related protein. Our previous study had shown that knockdown of HIP1R induces a dramatic decrease of dendritic gro...
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2018.00447/full |
| _version_ | 1811253569338212352 |
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| author | Qian Yang Lin Peng Yu Wu Yanan Li Ling Wang Jian-hong Luo Junyu Xu |
| author_facet | Qian Yang Lin Peng Yu Wu Yanan Li Ling Wang Jian-hong Luo Junyu Xu |
| author_sort | Qian Yang |
| collection | DOAJ |
| description | Huntington-interacting protein 1-related protein (HIP1R) was identified on the basis of its structural homology with HIP1. Based on its domain structure, HIP1R is a putative endocytosis-related protein. Our previous study had shown that knockdown of HIP1R induces a dramatic decrease of dendritic growth and branching in cultured rat hippocampal neurons. However, the underlying mechanism remains elucidative. In this study, we found that knockdown of HIP1R impaired the endocytosis of activated epidermal growth factor receptor (EGFR) and the consequent activation of the downstream ERK and Akt proteins. Meanwhile, it blocked the EGF-induced dendritic outgrowth. We also showed that the HIP1R fragment, amino acids 633–822 (HIP1R633–822), interacted with EGFR and revealed a dominant negative effect in disrupting the HIP1R-EGFR interaction-mediated neuronal development. Collectively, these results reveal a novel mechanism that HIP1R plays a critical role in neurite initiation and dendritic branching in cultured hippocampal neurons via mediating the endocytosis of EGFR and downstream signaling. |
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| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-12T16:52:55Z |
| publishDate | 2018-12-01 |
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| spelling | doaj.art-986b69ac70b74c029754b291e34f69bc2022-12-22T03:24:21ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-12-011110.3389/fnmol.2018.00447397954Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic DevelopmentQian Yang0Lin Peng1Yu Wu2Yanan Li3Ling Wang4Jian-hong Luo5Junyu Xu6Department of Neurobiology, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Psychiatry, Jining Medical University, Jining, ChinaDepartment of Neurobiology, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Neurobiology, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Neurobiology, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Neurobiology, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, ChinaHuntington-interacting protein 1-related protein (HIP1R) was identified on the basis of its structural homology with HIP1. Based on its domain structure, HIP1R is a putative endocytosis-related protein. Our previous study had shown that knockdown of HIP1R induces a dramatic decrease of dendritic growth and branching in cultured rat hippocampal neurons. However, the underlying mechanism remains elucidative. In this study, we found that knockdown of HIP1R impaired the endocytosis of activated epidermal growth factor receptor (EGFR) and the consequent activation of the downstream ERK and Akt proteins. Meanwhile, it blocked the EGF-induced dendritic outgrowth. We also showed that the HIP1R fragment, amino acids 633–822 (HIP1R633–822), interacted with EGFR and revealed a dominant negative effect in disrupting the HIP1R-EGFR interaction-mediated neuronal development. Collectively, these results reveal a novel mechanism that HIP1R plays a critical role in neurite initiation and dendritic branching in cultured hippocampal neurons via mediating the endocytosis of EGFR and downstream signaling.https://www.frontiersin.org/article/10.3389/fnmol.2018.00447/fullHIP1Rneurite initiationdendritic branchingEGFRendocytosissignaling pathway |
| spellingShingle | Qian Yang Lin Peng Yu Wu Yanan Li Ling Wang Jian-hong Luo Junyu Xu Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development Frontiers in Molecular Neuroscience HIP1R neurite initiation dendritic branching EGFR endocytosis signaling pathway |
| title | Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development |
| title_full | Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development |
| title_fullStr | Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development |
| title_full_unstemmed | Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development |
| title_short | Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development |
| title_sort | endocytic adaptor protein hip1r controls intracellular trafficking of epidermal growth factor receptor in neuronal dendritic development |
| topic | HIP1R neurite initiation dendritic branching EGFR endocytosis signaling pathway |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2018.00447/full |
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