Subcellular distribution affects BAG1 function

• Published in: Brain research Vol. 1198; pp. 21 - 26
• Main Authors: Liman, Jan, Faida, Lena, Dohm, Christoph P, Reed, John C, Bähr, Mathias, Kermer, Pawel
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 10-03-2008; Amsterdam Elsevier; New York, NY
• Subjects: Active Transport, Cell Nucleus - physiology; Animals; Apoptosis; BAG1; Biological and medical sciences; Brain - cytology; Brain - embryology; Brain - metabolism; Cell Compartmentation - physiology; Cell Death - physiology; Cell Differentiation - physiology; Cell Line, Transformed; Cell Nucleus - metabolism; Cell Nucleus - ultrastructure; Cytoprotection - physiology; Cytosol - metabolism; Development. Senescence. Regeneration. Transplantation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Fundamental and applied biological sciences. Psychology; Gene Transfer Techniques; Hsp70; HSP70 Heat-Shock Proteins - metabolism; Neurology; Neuronal differentiation; Neurons - cytology; Neurons - metabolism; Neuroprotection; NLS; Proto-Oncogene Proteins c-raf - metabolism; Rats; Stem Cells - cytology; Stem Cells - metabolism; Substantia Nigra - cytology; Substantia Nigra - embryology; Substantia Nigra - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Vertebrates: nervous system and sense organs; Neuronal differentiation; Neuroprotection; Hsp70; NLS; BAG1; Apoptosis; Cell death; Distribution; Heat shock protein; Nervous system; Differentiation
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.01.010

Abstract BAG1 is a potent neuroprotectant as well as a marker of differentiation in neuronal cells. It is known that BAG1 mainly localizes to the nucleus during neuronal development, whereas BAG1 shifts to the cytosol upon neuronal differentiation suggesting that distinct BAG1 functions depend on its subcellular localization. Here, we show that forced BAG1 expression within the nucleus when compared to full-length BAG1 expression and to control cells completely abolishes the neuroprotective effects of BAG1 supporting the notion that cytosolic interaction with Hsp70 is mandatory for BAG1 mediated neuroprotection. At the same time, we observed that cells can no longer differentiate into post-mitotic neurons when BAG1 is only present in the nucleus. In addition, phospho-Erk levels are decreased in those cells indicating that BAG1 has to translocate to the cytosol for Raf-dependent MAPK activation.