Subcellular distribution affects BAG1 function

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 it...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0006-8993 1872-6240
DOI:	10.1016/j.brainres.2008.01.010