The Binary Interacting Network of the Conserved Oligomeric Golgi Tethering Complex

Loh, Eva; Hong, Wanjin

doi:10.1074/jbc.m400662200

Cited by 56 publications

(58 citation statements)

References 29 publications

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“…This mutation results in the use of an alternative splice site ultimately leading to a premature stop codon [3]. A similar biochemical and clinical phenotype is seen between the previous North African Cog7 patients [3,8] and this patient. No material was unavailable for further testing from any of the patients or their families.…”

Section: Sequence Analysis Of Cog7supporting

confidence: 77%

“…An alternative model has been proposed by Loh et al This model suggests that two sub complexes are formed and that Cog4 drives the formation of these complexes. [8] This complex facilitates transport within the Golgi and retrograde transport from the Golgi to ER. Mutations of different subunits disrupt Golgi integrity and retrograde trafficking of the glycosylation machinery [3].…”

Section: Introductionmentioning

confidence: 99%

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Molecular and clinical characterization of a Moroccan Cog7 deficient patient

Kranz

Hagebeuk

et al. 2007

Molecular Genetics and Metabolism

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Mutations in the N-linked glycosylation pathway cause rare autosomal recessive defects known as Congenital Disorders of Glycosylation (CDG). A previously reported mutation in the Conserved Oligomeric Golgi complex gene, COG7, defined a new subtype of CDG in a Tunisian family. The mutation disrupted the hetero-octomeric COG complex and altered both N-and O-linked glycosylation. Here we present clinical and biochemical data from a second family with the same mutation.

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Section: Sequence Analysis Of Cog7supporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Molecular and clinical characterization of a Moroccan Cog7 deficient patient

Kranz

Hagebeuk

et al. 2007

Molecular Genetics and Metabolism

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“…Moreover Cog5-8p continue to localize properly to membranes in a juxtanuclear region. These data support our original model proposing two-lobed COG complex structure Loh and Hong, 2004) and suggests that Lobe B (COGs 5-8) may be attached to the Golgi membrane by its own receptor.…”

Section: Discussionsupporting

confidence: 77%

Role of Conserved Oligomeric Golgi Complex in the Abnormalities of Glycoprotein Processing in Breast Cancer Cells

Zolov¹

2006

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. (From -To) 5f. WORK UNIT NUMBER REPORT DATE (DD-MM-YYYY) 01-05-2006 REPORT TYPE Annual Summary DATES COVERED PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERUniversity of Arkansas Little Rock, Arkansas 72205 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe conserved oligomeric Golgi (COG) complex consists of eight subunits that are thought to be involved in vesicle tethering. Available mutants with the mutations in COG complex subunits exhibit defects in basic Golgi functions: protein glycosylation and its sorting. For analysis of COG complex function we utilized RNA interference assay to knockdown COG3p subunit of COG complex in normal and breast cancer cells and other tumor cell lines. Acute knockdown of the COG3 was accompanied by reduction in Cog1, 2 and 4 protein levels, rapid Golgi fragmentation and accumulation of COG complex dependent (CCD) vesicles. Constantly cycling medial-Golgi enzymes are transported from distal compartments in CCD vesicles. Dysfunction of COG complex leads to separation of glycosyltransferases from anterograde cargo molecules passing along secretory pathway, thus affecting normal protein glycosylation. Altered level of COG3p (or COG complex) expression could be a common feature of cancer cells defective in protein trafficking and Golgi modifications. The importance of the COG complex for both function and architecture of the Golgi apparatus does not depend on cell type. Partial malfunction of the COG complex may play a role in establishing of cancer phenotype. SUBJECT TERMS IntroductionIn breast, colon and skin cancers, the unusual production and secretion of aberrantly glycosylated proteins and lipids on the surface are associated with disease progression, metastasis and poor clinical outcome (1). Glycosylation abnormalities concern both N-linked and O-linked carbohyd...

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“…Despite progress in characterizing the structures of individual COG/Dsl1p/exocyst subunits, relatively little is known about how the subunits within each complex interact with one another (32,(34)(35)(36). One exception is the Dsl1p and Tip20p subunits of the Dsl1p complex, which were recently shown to interact via N-terminal ␣-helices (20).…”

Section: Discussionmentioning

confidence: 99%

Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene

Richardson

Smith

Ungár

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The proper glycosylation of proteins trafficking through the Golgi apparatus depends upon the conserved oligomeric Golgi (COG) complex. Defects in COG can cause fatal congenital disorders of glycosylation (CDGs) in humans. The recent discovery of a form of CDG, caused in part by a COG4 missense mutation changing Arg 729 to Trp, prompted us to determine the 1.9 Å crystal structure of a Cog4 C-terminal fragment. Arg 729 is found to occupy a key position at the center of a salt bridge network, thereby stabilizing Cog4's small C-terminal domain. Studies in HeLa cells reveal that this C-terminal domain, while not needed for the incorporation of Cog4 into COG complexes, is essential for the proper glycosylation of cell surface proteins. We also find that Cog4 bears a strong structural resemblance to exocyst and Dsl1p complex subunits. These complexes and others have been proposed to function by mediating the initial tethering between transport vesicles and their membrane targets; the emerging structural similarities provide strong evidence of a common evolutionary origin and may reflect shared mechanisms of action.congenital disorder of glycosylation ͉ Golgi apparatus ͉ multi-subunit tethering complex ͉ vesicle trafficking ͉ X-ray crystallography M ultiple lines of evidence implicate the conserved oligomeric Golgi (COG) complex in retrograde transport within the Golgi apparatus (1, 2). For example, partial knockdown of mammalian COG3 permitted exocytosis, while simultaneously blocking the retrograde transport of Shiga toxin from endosomes to the ER (3). COG was initially isolated from bovine brain on the basis of its ability to stimulate an in vitro Golgi transport assay (4). Two of its 8 subunits, Cog1/ldlB and Cog2/ ldlC, had previously been identified in a genetic screen for compromised cell surface receptor stability (5, 6). In the yeast Saccharomyces cerevisiae, the COG complex was discovered through studies of one of its subunits, Cog8p/Dor1p. Implicated in vesicle targeting to the Golgi apparatus, Cog8p was found to co-immunoprecipitate with 7 other polypeptides (7). The 7 associated polypeptides included two (Cog2p/Sec35p and Cog3p/ Sec34p) that had earlier been identified in genetic screens for temperature-sensitive mutations causing secretion defects (8). In further support of a role in trafficking to and within the Golgi, COG interacts physically with a large number of Golgi-localized trafficking factors, including (in yeast) the Rab family G protein Ypt1p, the SNAREs Sed5p, Ykt6p, Gos1p, and Sec22p, and COPI vesicle coat proteins (9).COG is one of several large protein complexes proposed to function as multisubunit tethering factors, mediating the initial interaction between transport vesicles and their target membranes (2, 10-12). For many of these complexes, a dearth of structural information has slowed the development of mechanistic models and has made it difficult to know how-or whether-to apply lessons learned from studies of one complex to another. Subunits of the COG, exocyst, Dsl1p, and Golgiassoci...

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The Binary Interacting Network of the Conserved Oligomeric Golgi Tethering Complex

Cited by 56 publications

References 29 publications

Molecular and clinical characterization of a Moroccan Cog7 deficient patient

Molecular and clinical characterization of a Moroccan Cog7 deficient patient

Role of Conserved Oligomeric Golgi Complex in the Abnormalities of Glycoprotein Processing in Breast Cancer Cells

Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene

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