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PMID:22139372

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Citation

Bräutigam, L, Schütte, LD, Godoy, JR, Prozorovski, T, Gellert, M, Hauptmann, G, Holmgren, A, Lillig, CH and Berndt, C (2011) Vertebrate-specific glutaredoxin is essential for brain development. Proc. Natl. Acad. Sci. U.S.A. 108:20532-7

Abstract

Cellular functions and survival are dependent on a tightly controlled redox potential. Currently, an increasing amount of data supports the concept of local changes in the redox environment and specific redox signaling events controlling cell function. Specific protein thiol groups are the major targets of redox signaling and regulation. Thioredoxins and glutaredoxins catalyze reversible thiol-disulfide exchange reactions and are primary regulators of the protein thiol redox state. Here, we demonstrate that embryonic brain development depends on the enzymatic activity of glutaredoxin 2. Zebrafish with silenced expression of glutaredoxin 2 lost virtually all types of neurons by apoptotic cell death and the ability to develop an axonal scaffold. As demonstrated in zebrafish and in a human cellular model for neuronal differentiation, glutaredoxin 2 controls axonal outgrowth via thiol redox regulation of collapsin response mediator protein 2, a central component of the semaphorin pathway. This study provides an example of a specific thiol redox regulation essential for vertebrate embryonic development.

Links

PubMed PMC3251147 Online version:10.1073/pnas.1110085108

Keywords

Animals; Apoptosis; Axons/physiology; Brain/embryology; Cell Line, Tumor; Developmental Biology; Gene Expression Regulation, Developmental; Glutaredoxins/chemistry; Glutaredoxins/genetics; Humans; Neurites/metabolism; Oxidation-Reduction; Recombinant Proteins/chemistry; Signal Transduction; Vertebrates; Zebrafish/embryology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:A0A0R4IFC0

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:A0A0R4IFC0

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120127-9

P

Seeded From UniProt

complete

DANRE:A0A0R4IFC0

enables

GO:0016491: oxidoreductase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:A0A0R4ILJ8

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:A0A0R4ILJ8

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120127-9

P

Seeded From UniProt

complete

DANRE:A0A0R4ILJ8

enables

GO:0016491: oxidoreductase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:A0A0R4IXU6

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:A0A0R4IXU6

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120127-9

P

Seeded From UniProt

complete

DANRE:A0A0R4IXU6

enables

GO:0016491: oxidoreductase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DANRE:A0A2R8QFM8

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:A8DZ95

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:Q52PJ3

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:Q6DH06

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DANRE:Q6DH06

involved_in

GO:0007417: central nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-120127-9

P

Seeded From UniProt

complete

DANRE:Q6DH06

enables

GO:0016491: oxidoreductase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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