The Liver Connexin32 Interactome Is a Novel Plasma Membrane-Mitochondrial Signaling Nexus
文献类型：期刊论文
| 作者 | Fowler, Stephanie L.1,3; Akins, Mark1,3; Zhou, Hu2 ; Figeys, Daniel; Bennett, Steffany A. L.1,3
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| 刊名 | JOURNAL OF PROTEOME RESEARCH
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| 出版日期 | 2013-06 |
| 卷号 | 12期号:6页码:2597-2610 |
| 关键词 | gap junction connexin connexin32 connexin26 mitochondria interactome sideroflexin mass spectrometry immunoprecipitation inner mitochondrial membrane |
| ISSN号 | 1535-3893 |
| DOI | 10.1021/pr301166p |
| 文献子类 | Article |
| 英文摘要 | Connexins are the structural subunits of gap junctions and act as protein platforms for signaling complexes. Little is known about tissue-specific connexin signaling nexuses, given significant challenges associated with affinity-purifying endogenous channel complexes to the level required for interaction analyses. Here, we used multiple subcellular fractionation techniques to isolate connexin32-enriched membrane microdomains from murine liver. We show, for the first time, that connexin32 localizes to both the plasma membrane and inner mitochondrial membrane of hepatocytes. Using a combination of immunoprecipitation-high throughput mass spectrometry, reciprocal co-IP, and subcellular fractionation methodologies, we report a novel interactome validated using null mutant controls. Eighteen connexin32 interacting proteins were identified. The majority represent resident mitochondrial proteins, a minority represent plasma membrane, endoplasmic reticulum, or cytoplasmic partners. In particular, connexin32 interacts with connexin26 and the mitochondrial protein, sideroflexin-1, at the plasma membrane. Connexin32 interaction enhances connexin26 stability. Converging bioinformatic, biochemical, and confocal analyses support a role for connexin32 in transiently tethering mitochondria to connexin32-enriched plasma membrane microdomains through interaction with proteins in the outer mitochondrial membrane, including sideroflexin-1. Complex formation increases the pool of sideroflexin-1 that is present at the plasma membrane. Together, these data identify a novel plasma membrane/mitochondrial signaling nexus in the connexin32 interactome. |
| WOS关键词 | ADENINE-NUCLEOTIDE TRANSLOCATOR ; JUNCTIONAL INTERCELLULAR COMMUNICATION ; GAP-JUNCTIONS ; SIDEROFLEXIN FAMILY ; RAT HEPATOCYTES ; PROTEINS ; MOUSE ; DOMAINS ; GENES ; EXPRESSION |
| 资助项目 | CIHR[MOP 62826] ; CIHR Training Program in Neurodegenerative Lipidomics (CTPNL)[TGF 96121] ; Institute of Aging[00000000] ; CTPNL[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000320298600023 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277608]  |
| 专题 | 分析化学研究室 |
| 通讯作者 | Figeys, Daniel |
| 作者单位 | 1.Univ Ottawa, Neural Regenerat Lab, Ottawa, ON, Canada; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 3.Univ Ottawa, Ottawa Inst Syst Biol, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada; |
| 推荐引用方式 GB/T 7714 | Fowler, Stephanie L.,Akins, Mark,Zhou, Hu,et al. The Liver Connexin32 Interactome Is a Novel Plasma Membrane-Mitochondrial Signaling Nexus[J]. JOURNAL OF PROTEOME RESEARCH,2013,12(6):2597-2610. |
| APA | Fowler, Stephanie L.,Akins, Mark,Zhou, Hu,Figeys, Daniel,&Bennett, Steffany A. L..(2013).The Liver Connexin32 Interactome Is a Novel Plasma Membrane-Mitochondrial Signaling Nexus.JOURNAL OF PROTEOME RESEARCH,12(6),2597-2610. |
| MLA | Fowler, Stephanie L.,et al."The Liver Connexin32 Interactome Is a Novel Plasma Membrane-Mitochondrial Signaling Nexus".JOURNAL OF PROTEOME RESEARCH 12.6(2013):2597-2610. |
入库方式： OAI收割
来源：上海药物研究所
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