title: Regulation of basal autophagy by transient receptor potential melastatin 7 (TRPM7) channel.
abstract: Macroautophagy (hereafter referred to as autophagy) is a catabolic process for the degradation and recycling of cellular components. Autophagy digests intracellular components, recycling material subsequently used for new protein synthesis. The Ca(2+)- and Mg(2+)-permeable transient receptor potential melastatin 7 (TRPM7) channel underlies the constitutive Ca(2+) influx in some cells. Since autophagy is regulated by cytosolic Ca(2+) level, we set out to determine whether Ca(2+) influx through the TRPM7 channel regulates basal autophagy. When TRPM7 channel expression was induced from HEK293 cells in a nutrient-rich condition, LC3-II level increased indicating the increased level of basal autophagy. The effect of TRPM7 channel on basal autophagy was via Ca(2+)/calmodulin-dependent protein kinase kinase β, and AMP-activated protein kinase pathway. In contrast, the level of basal autophagy was decreased when the endogenous TRPM7 channel in SH-SY5Y cells was down-regulated using short hairpin RNA. Similarly, an inhibitor for TRPM7 channel decreased the level of basal autophagy. In addition, the inhibitory effect of channel inhibitor on basal autophagy was reversed by increasing extracellular Ca(2+)concentration, suggesting that Ca(2+) influx through TRPM7 channel directly links to basal autophagy. Thus, our studies demonstrate the new role of TRPM7 channel-mediated Ca(2+) entry in the regulation of basal autophagy.
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Hyun Geun
authors.initials: HG
authors.lastname: Oh
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Yoon Sun
authors.initials: YS
authors.lastname: Chun
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
authors.forename: Chul-Seung
authors.initials: CS
authors.lastname: Park
authors.affiliation: Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Tae-Wan
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Myoung Kyu
authors.initials: MK
authors.lastname: Park
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea. Electronic address: schung@skku.edu.
authors.forename: Sungkwon
authors.initials: S
authors.lastname: Chung
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D020013:Calcium Signaling; D002460:Cell Line; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016296:Mutagenesis; D018408:Patch-Clamp Techniques; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Autophagy; CaMKKβ; Parkinson's disease; TRPM7 channel