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PMID:24768539

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Citation

Yuan, WC, Lee, YR, Lin, SY, Chang, LY, Tan, YP, Hung, CC, Kuo, JC, Liu, CH, Lin, MY, Xu, M, Chen, ZJ and Chen, RH (2014) K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking. Mol. Cell 54:586-600

Abstract

Ubiquitin chains are formed as structurally distinct polymers via different linkages, and several chain types including K33-linkage remain uncharacterized. Here, we describe a role for K33-polyubiquitination in protein trafficking. We show that the Cullin 3 (Cul3) substrate adaptor KLHL20 is localized to the trans-Golgi network (TGN) and is important for post-Golgi trafficking by promoting the biogenesis of TGN-derived transport carriers. The Cul3-KLHL20 ubiquitin E3 ligase catalyzes a nondegradable, K33-linked polyubiquitination on coronin 7 (Crn7), which facilitates Crn7 targeting to TGN through a ubiquitin-dependent interaction with Eps15. Blockage of K33-chain formation, Crn7 ubiquitination, or disruption of Crn7-Eps15 interaction impairs TGN-pool F-actin assembly, a process essential for generating transport carriers. Enforced targeting of Crn7 to TGN bypasses the requirement of K33-ubiquitination for TGN-pool F-actin assembly and post-Golgi trafficking. Our study reveals a role of KLHL20-mediated K33-ubiquitination of Crn7 in post-Golgi transport and identifies a cellular recognition mechanism for this ubiquitin chain type.

Links

PubMed Online version:10.1016/j.molcel.2014.03.035

Keywords

Actins/genetics; Actins/metabolism; Adaptor Proteins, Vesicular Transport/genetics; Adaptor Proteins, Vesicular Transport/metabolism; Animals; COS Cells; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; Cercopithecus aethiops; Cullin Proteins/genetics; Cullin Proteins/metabolism; Golgi Apparatus/metabolism; HEK293 Cells; HeLa Cells; Humans; Lysine/metabolism; Microfilament Proteins/genetics; Microfilament Proteins/metabolism; Protein Transport; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism; Ubiquitination; trans-Golgi Network/metabolism

Significance

Annotations

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

HUMAN:EPS15

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P57737

F

Seeded From UniProt

complete

HUMAN:CORO7

enables

GO:0003779: actin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CORO7

located_in

GO:0005802: trans-Golgi network

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CORO7

involved_in

GO:0030041: actin filament polymerization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CORO7

involved_in

GO:0006895: Golgi to endosome transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CORO7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9Y2M5

F

Seeded From UniProt

complete

HUMAN:CORO7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P42566

F

Seeded From UniProt

complete

HUMAN:ZRAN1

involved_in

GO:1990168: protein K33-linked deubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KLH20

part_of

GO:0031463: Cul3-RING ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:KLH20

located_in

GO:0005802: trans-Golgi network

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:KLH20

involved_in

GO:1990390: protein K33-linked ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KLH20

contributes_to

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:KLH20

involved_in

GO:0006895: Golgi to endosome transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KLH20

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P57737

F

Seeded From UniProt

complete

HUMAN:EPS15

enables

GO:0031593: polyubiquitin modification-dependent protein binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:EPS15

involved_in

GO:0006895: Golgi to endosome transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CUL3

part_of

GO:0031463: Cul3-RING ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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