Sac1-Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus.

Sac1 is a phosphoinositide phosphatase of the endoplasmic reticulum and Golgi apparatus that controls organelle membrane composition principally via regulation of phosphatidylinositol 4-phosphate signaling. We present a characterization of the structure of the N-terminal portion of yeast Sac1, containing the conserved Sac1 homology domain, in complex with Vps74, a phosphatidylinositol ...
4-kinase effector and the orthologue of human GOLPH3. The interface involves the N-terminal subdomain of the Sac1 homology domain, within which mutations in the related Sac3/Fig4 phosphatase have been linked to Charcot-Marie-Tooth disorder CMT4J and amyotrophic lateral sclerosis. Disruption of the Sac1-Vps74 interface results in a broader distribution of phosphatidylinositol 4-phosphate within the Golgi apparatus and failure to maintain residence of a medial Golgi mannosyltransferase. The analysis prompts a revision of the membrane-docking mechanism for GOLPH3 family proteins and reveals how an effector of phosphoinositide signaling serves a dual function in signal termination.
Mesh Terms:
Carrier Proteins, Catalysis, Crystallography, X-Ray, Endoplasmic Reticulum, Golgi Apparatus, Green Fluorescent Proteins, Membrane Proteins, Models, Molecular, Multiprotein Complexes, Phosphatidylinositol Phosphates, Phosphoric Monoester Hydrolases, Protein Binding, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
J. Cell Biol.
Date: Aug. 18, 2014
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