Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells

Rudolf Götz; Stefan Wiese; Shinichi Takayama; Guadalupe C. Camarero; Wilfried Rossoll; Ulrich Schweizer; Jakob Troppmair; Sibylle Jablonka; Bettina Holtmann; John C. Reed; Ulf R. Rapp; Michael Sendtner

doi:10.1038/nn1524

Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells

Rudolf Götz, Stefan Wiese, Shinichi Takayama, Guadalupe C. Camarero, Wilfried Rossoll, Ulrich Schweizer, Jakob Troppmair, Sibylle Jablonka, Bettina Holtmann, John C. Reed, Ulf R. Rapp, Michael Sendtner

Neuroscience

Research output: Contribution to journal › Article › peer-review

98 Scopus citations

Abstract

Bag1 is a cochaperone for the heat-shock protein Hsp70 that interacts with C-Raf, B-Raf, Akt, Bcl-2, steroid hormone receptors and other proteins. Here we use targeted gene disruption in mice to show that Bag1 has an essential role in the survival of differentiating neurons and hematopoietic cells. Cells of the fetal liver and developing nervous system in Bag1^-/- mice underwent massive apoptosis. Lack of Bag1 did not disturb the primary function of Akt or Raf, as phosphorylation of the forkhead transcription factor FKHR and activation of extracellular signal-regulated kinase (Erk)-1/2 were not affected. However, the defect was associated with the disturbance of a tripartite complex formed by Akt, B-Raf and Bag1, in addition to the absence of Bad phosphorylation at Ser136. We also observed reduced expression of members of the inhibitor of apoptosis (IAP) family. Our data show that Bag1 is a physiological mediator of extracellular survival signals linked to the cellular mechanisms that prevent apoptosis in hematopoietic and neuronal progenitor cells.

Original language	English (US)
Pages (from-to)	1169-1178
Number of pages	10
Journal	Nature Neuroscience
Volume	8
Issue number	9
DOIs	https://doi.org/10.1038/nn1524
State	Published - Sep 2005

ASJC Scopus subject areas

General Neuroscience

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10.1038/nn1524

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@article{46503c2ab53a4b0abad88120b997c360,

title = "Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells",

abstract = "Bag1 is a cochaperone for the heat-shock protein Hsp70 that interacts with C-Raf, B-Raf, Akt, Bcl-2, steroid hormone receptors and other proteins. Here we use targeted gene disruption in mice to show that Bag1 has an essential role in the survival of differentiating neurons and hematopoietic cells. Cells of the fetal liver and developing nervous system in Bag1-/- mice underwent massive apoptosis. Lack of Bag1 did not disturb the primary function of Akt or Raf, as phosphorylation of the forkhead transcription factor FKHR and activation of extracellular signal-regulated kinase (Erk)-1/2 were not affected. However, the defect was associated with the disturbance of a tripartite complex formed by Akt, B-Raf and Bag1, in addition to the absence of Bad phosphorylation at Ser136. We also observed reduced expression of members of the inhibitor of apoptosis (IAP) family. Our data show that Bag1 is a physiological mediator of extracellular survival signals linked to the cellular mechanisms that prevent apoptosis in hematopoietic and neuronal progenitor cells.",

author = "Rudolf G{\"o}tz and Stefan Wiese and Shinichi Takayama and Camarero, {Guadalupe C.} and Wilfried Rossoll and Ulrich Schweizer and Jakob Troppmair and Sibylle Jablonka and Bettina Holtmann and Reed, {John C.} and Rapp, {Ulf R.} and Michael Sendtner",

note = "Funding Information: We thank M. Pfister, J. Marcano and K. Kalus for excellent technical assistance; R. McKay (US National Institutes of Health) for providing the nestin-specific antibody; T. Jessell for providing the islet-1/2 hybridoma (39.4D5) through the Developmental Studies Hybridoma Bank; and R. Timpl for the kind donation of laminin. This work was supported by the Deutsche Forschungsgemeinschaft (SE 697/3-3, SFB487, TP C4 and SFB581 TP B4 and B17), the US National Institutes of Health (CA67385) and the Hermann and Lilly Schilling Foundation.",

year = "2005",

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doi = "10.1038/nn1524",

language = "English (US)",

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T1 - Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells

AU - Götz, Rudolf

AU - Wiese, Stefan

AU - Takayama, Shinichi

AU - Camarero, Guadalupe C.

AU - Rossoll, Wilfried

AU - Schweizer, Ulrich

AU - Troppmair, Jakob

AU - Jablonka, Sibylle

AU - Holtmann, Bettina

AU - Reed, John C.

AU - Rapp, Ulf R.

AU - Sendtner, Michael

N1 - Funding Information: We thank M. Pfister, J. Marcano and K. Kalus for excellent technical assistance; R. McKay (US National Institutes of Health) for providing the nestin-specific antibody; T. Jessell for providing the islet-1/2 hybridoma (39.4D5) through the Developmental Studies Hybridoma Bank; and R. Timpl for the kind donation of laminin. This work was supported by the Deutsche Forschungsgemeinschaft (SE 697/3-3, SFB487, TP C4 and SFB581 TP B4 and B17), the US National Institutes of Health (CA67385) and the Hermann and Lilly Schilling Foundation.

PY - 2005/9

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N2 - Bag1 is a cochaperone for the heat-shock protein Hsp70 that interacts with C-Raf, B-Raf, Akt, Bcl-2, steroid hormone receptors and other proteins. Here we use targeted gene disruption in mice to show that Bag1 has an essential role in the survival of differentiating neurons and hematopoietic cells. Cells of the fetal liver and developing nervous system in Bag1-/- mice underwent massive apoptosis. Lack of Bag1 did not disturb the primary function of Akt or Raf, as phosphorylation of the forkhead transcription factor FKHR and activation of extracellular signal-regulated kinase (Erk)-1/2 were not affected. However, the defect was associated with the disturbance of a tripartite complex formed by Akt, B-Raf and Bag1, in addition to the absence of Bad phosphorylation at Ser136. We also observed reduced expression of members of the inhibitor of apoptosis (IAP) family. Our data show that Bag1 is a physiological mediator of extracellular survival signals linked to the cellular mechanisms that prevent apoptosis in hematopoietic and neuronal progenitor cells.

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Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells

Abstract

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