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Vol. 17, Issue 5, 2312-2321, May 2006

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COG-7-deficient Human Fibroblasts Exhibit Altered Recycling of Golgi Proteins

Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110

Submitted September 1, 2005; Revised January 23, 2006; Accepted February 16, 2006
Monitoring Editor: Jennifer Lippincott-Schwartz

Recently, we reported that two siblings presenting with the clinical syndrome congenital disorders of glycosylation (CDG) have mutations in the gene encoding Cog7p, a member of the conserved oligomeric Golgi (COG) complex. In this study, we analyzed the localization and trafficking of multiple Golgi proteins in patient fibroblasts under a variety of conditions. Although the immunofluorescent staining pattern of several Golgi proteins was indistinguishable from normal, the staining of endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC)-53 and the vesicular-soluble N-ethylmaleimide-sensitive factor attachment protein receptors GS15 and GS28 was abnormal, and the steady-state level of GS15 was greatly decreased. Retrograde transport of multiple Golgi proteins to the ER in patient fibroblasts via brefeldin A-induced tubules was significantly slower than occurs in normal fibroblasts, whereas anterograde protein trafficking was much less affected. After prolonged treatment with brefeldin A, several Golgi proteins were detected in clusters that colocalize with the microtubule-organizing center in patient cells. All of these abnormalities were normalized in COG7-corrected patient fibroblasts. These results serve to better define the role of the COG complex in facilitating protein trafficking between the Golgi and ER and provide a diagnostic framework for the identification of CDG defects involving trafficking proteins.

Abbreviations used: GalT, 1,4-galactosyltransferase; BFA, brefeldin A; CDG, congenital disorders of glycosylation; COG, conserved oligomeric Golgi; ER, endoplasmic reticulum; ERGIC, ER-Golgi intermediate compartment; MTOC, microtubule-organizing center.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Richard Steet (rsteet{at}im.wustl.edu) or Stuart Kornfeld (skornfel{at}im.wustl.edu).

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