The role of GOLPH3 in COPI coated vesicle cargo selection

Presenting author: Rebecca Taylor

Max Planck Institute of Biochemistry, Cell and Virus Structure, Am Klopferspitz 18, 81475 Martinsried [DE], taylor@biochem.mpg.de

Author(s):
Rebecca Taylor

COPI coated vesicles mediate transport from the Golgi to the ER and transport within the Golgi. Distinct sets of cargo are transported between these different locations. Therefore, mechanisms of cargo selection must allow incorporation of specific cargo at different locations in the Golgi. Cargo selection is mediated by direct binding to the COPI vesicle coat or by binding to a cargo receptor that binds the coat. Transport to the ER involves direct COPI-binding via a C-terminal K(x)Kxx motif in the cytoplasmic tails of many ER residents or indirect binding of C-terminal ‘KDEL’ sequences to the KDEL receptor which binds to COPI. The recognition mechanism for intra-Golgi cargo is less well-understood. GOLPH3 is proposed to function as a cargo receptor for Golgi enzymes as it binds COPI, the cytosolic tails of some Golgi enzymes, and the Golgi-localized lipid PI4P. Here we determined the cryo-ET structure of in vitro reconstituted COPI vesicles bound to GOLPH3. GOLPH3 is present as a stoichiometric component of the coat, bound close to the membrane in a position that occludes a binding site for ER-resident cargo. Mutation of clusters of residues on the membrane-facing interface of GOLPH3 results in loss of retention of Golgi residents, and different mutations affect different residents. These results provide insight into how COPI vesicles selectively transport Golgi proteins and provide an explanation for why retention signals for Golgi residents have been hard to define.

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