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The integral membrane protein ITM2A, a transcriptional target of PKA-CREB, regulates autophagic flux via interaction with the vacuolar ATPase.
- Source :
-
Autophagy [Autophagy] 2015; Vol. 11 (5), pp. 756-68. - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Gene Silencing
HEK293 Cells
HeLa Cells
Humans
Lysosomes metabolism
Models, Biological
Phagosomes metabolism
Promoter Regions, Genetic genetics
Protein Binding
Signal Transduction
Autophagy
Cyclic AMP Response Element-Binding Protein metabolism
Cyclic AMP-Dependent Protein Kinases metabolism
Membrane Proteins metabolism
Transcription, Genetic
Vacuolar Proton-Translocating ATPases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1554-8635
- Volume :
- 11
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Autophagy
- Publication Type :
- Academic Journal
- Accession number :
- 25951193
- Full Text :
- https://doi.org/10.1080/15548627.2015.1034412