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PMID:22451918

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Citation

Delgehyr, N, Wieland, U, Rangone, H, Pinson, X, Mao, G, Dzhindzhev, NS, McLean, D, Riparbelli, MG, Llamazares, S, Callaini, G, Gonzalez, C and Glover, DM (2012) Drosophila Mgr, a Prefoldin subunit cooperating with von Hippel Lindau to regulate tubulin stability. Proc. Natl. Acad. Sci. U.S.A. 109:5729-34

Abstract

Mutations in Drosophila merry-go-round (mgr) have been known for over two decades to lead to circular mitotic figures and loss of meiotic spindle integrity. However, the identity of its gene product has remained undiscovered. We now show that mgr encodes the Prefoldin subunit counterpart of human von Hippel Lindau binding-protein 1. Depletion of Mgr from cultured cells also leads to formation of monopolar and abnormal spindles and centrosome loss. These phenotypes are associated with reductions of tubulin levels in both mgr flies and mgr RNAi-treated cultured cells. Moreover, mgr spindle defects can be phenocopied by depleting β-tubulin, suggesting Mgr function is required for tubulin stability. Instability of β-tubulin in the mgr larval brain is less pronounced than in either mgr testes or in cultured cells. However, expression of transgenic β-tubulin in the larval brain leads to increased tubulin instability, indicating that Prefoldin might only be required when tubulins are synthesized at high levels. Mgr interacts with Drosophila von Hippel Lindau protein (Vhl). Both proteins interact with unpolymerized tubulins, suggesting they cooperate in regulating tubulin functions. Accordingly, codepletion of Vhl with Mgr gives partial rescue of tubulin instability, monopolar spindle formation, and loss of centrosomes, leading us to propose a requirement for Vhl to promote degradation of incorrectly folded tubulin in the absence of functional Prefoldin. Thus, Vhl may play a pivotal role: promoting microtubule stabilization when tubulins are correctly folded by Prefoldin and tubulin destruction when they are not.

Links

PubMed PMC3326472 Online version:10.1073/pnas.1108537109

Keywords

Animals; Conserved Sequence; Drosophila Proteins/metabolism; Drosophila melanogaster/cytology; Drosophila melanogaster/metabolism; Humans; Microtubules/metabolism; Mitotic Spindle Apparatus/metabolism; Molecular Chaperones/metabolism; Mutation/genetics; Protein Binding; Protein Stability; Protein Subunits/metabolism; Proteolysis; Tubulin/metabolism; Von Hippel-Lindau Tumor Suppressor Protein/metabolism

Significance

Annotations

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

DROME:VHL

involved_in

GO:0007098: centrosome cycle

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0264694

P

Seeded From UniProt

complete

DROME:VHL

involved_in

GO:0090307: mitotic spindle assembly

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0264694

P

Seeded From UniProt

complete

DROME:PFD3

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:PFD3

involved_in

GO:0007098: centrosome cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PFD3

involved_in

GO:0007017: microtubule-based process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PFD3

enables

GO:0048487: beta-tubulin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:PFD3

involved_in

GO:0090307: mitotic spindle assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PFD3

involved_in

GO:0090306: spindle assembly involved in meiosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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