PMID:22451918

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
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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

References

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