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J Cell Biol. 2014 Aug 18;206(4):485-91. doi: 10.1083/jcb.201404041. Epub 2014 Aug 11.

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

Author information

1
Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
2
Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520 christopher.burd@yale.edu karin.reinisch@yale.edu.

Abstract

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.

PMID:
25113029
PMCID:
PMC4137058
DOI:
10.1083/jcb.201404041
[Indexed for MEDLINE]
Free PMC Article

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