The integral membrane protein ITM2A, a transcriptional target of PKA-CREB, regulates autophagic flux via interaction with the vacuolar ATPase
| Autor: | Ik Soon Jang, Sim Namkoong, Kang I. Lee, Rackhyun Park, Junsoo Park, Eun-Ju Lee, Jin I. Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
tfLC3
tandem fluorescent-tagged LC3 v-ATPase vacuolar ATPase Transcription Genetic Phagosomes LAMP1 lysosomal-associated membrane protein 1 PKA SQSTM1 sequestosome 1 Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Integral membrane protein biology CREB BafA1 bafilomycin A1 Basic Research Paper Cell biology cAMP cyclic adenosine monophosphate ChIP chromatin immunoprecipitation v-ATPase CRE cAMP response element EBSS Earle's balanced salt solution Signal transduction Protein Binding Signal Transduction autophagy Vacuolar Proton-Translocating ATPases CREB cAMP responsive element binding protein MTOR mechanistic target of rapamycin ITM2A integral membrane protein 2A TPA 12-O-tetradecanoylphorbol-13-acetate Models Biological V-ATPase Humans Gene Silencing Molecular Biology MAP1LC3B/LC3B microtubule-associated protein 1 light chain 3 β Autophagy Membrane Proteins Cell Biology Cyclic AMP-Dependent Protein Kinases ITM2A HEK293 Cells Membrane protein biology.protein PKA protein kinase A Lysosomes Flux (metabolism) MAPK mitogen-activated protein kinase HeLa Cells |
| Zdroj: | Autophagy |
| ISSN: | 1554-8635 1554-8627 |
| Popis: | The PKA-CREB signaling pathway is involved in many cellular processes including autophagy. Recent studies demonstrated that PKA-CREB inhibits autophagy in yeast; however, the role of PKA-CREB signaling in mammalian cell autophagy has not been fully characterized. Here, we report that the integral membrane protein ITM2A expression is positively regulated by PKA-CREB signaling and ITM2A expression interferes with autophagic flux by interacting with vacuolar ATPase (v-ATPase). The ITM2A promoter contains a CRE element, and mutation at the CRE consensus site decreases the promoter activity. Forskolin treatment and PKA expression activate the ITM2A promoter confirming that ITM2A expression is dependent on the PKA-CREB pathway. ITM2A expression results in the accumulation of autophagosomes and interferes with autolysosome formation by blocking autophagic flux. We demonstrated that ITM2A physically interacts with v-ATPase and inhibits lysosomal function. These results support the notion that PKA-CREB signaling pathway regulates ITM2A expression, which negatively regulates autophagic flux by interfering with the function of v-ATPase. |
| Databáze: | OpenAIRE |
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