Giantin Explained

Giantin or Golgin subfamily B member 1 is a protein that in humans is encoded by the GOLGB1 gene.^{[1] [2] [3]} Giantin is located at the cis-medial rims of the Golgi apparatus and is part of the Golgi matrix that is responsible for membrane trafficking in secretory pathway of proteins. This function is key for proper localisation of proteins at the plasma membrane and outside the cell (extracellular region) which is important for cell function that is dependent on for example receptors and the extracellular matrix function. Recent animal model knockout studies of GOLGB1 in mice,^[4] rat,^[5] and zebrafish^[6] have shown that phenotypes are different between species ranging from mild to severe craniofacial defects in the rodent models to just minor size defects in zebrafish. However, in adult zebrafish a tumoral calcinosis-like phenotype was observed, and in humans such phenotype has been linked to defective glycosyltransferase function (e.g. GALNT3 protein).^[7]

Function and Interactions

Giantin is a disulfide-linked homodimer which contains several (around 37) coiled-coiled domains. GOLGB1 protein has been shown to interact with ACBD3 and with PLK3^[8] and vesicle tethering small GTPases Rab1 and Rab6.^[9] Giantin also interacts with P115 at the N-terminal coils facilitating binding to the other Golgi matrix protein GM130^[10] that is thought to be important for Golgi secretory function. Loss-of function studies of giantin have also suggested a role in primary cilia^{[11] [12]} function and defective regulation of glycosyltransferase expression and calcineurin signalling in tissue culture cells.^{[13] [14]}

Further reading

• Sohda M, Misumi Y, Fujiwara T . Molecular cloning and sequence analysis of a human 372-kDA protein localized in the Golgi complex. . Biochem. Biophys. Res. Commun. . 205 . 2 . 1399–408 . 1995 . 7802676 . 10.1006/bbrc.1994.2821 . etal.
• Seelig HP, Schranz P, Schröter H . Macrogolgin--a new 376 kD Golgi complex outer membrane protein as target of antibodies in patients with rheumatic diseases and HIV infections. . J. Autoimmun. . 7 . 1 . 67–91 . 1994 . 8198703 . 10.1006/jaut.1994.1006 . etal.
• Sönnichsen B, Lowe M, Levine T . A role for giantin in docking COPI vesicles to Golgi membranes. . J. Cell Biol. . 140 . 5 . 1013–21 . 1998 . 9490716 . 10.1083/jcb.140.5.1013 . 2132694 . etal.
• Linstedt AD, Jesch SA, Mehta A . Binding relationships of membrane tethering components. The giantin N terminus and the GM130 N terminus compete for binding to the p115 C terminus. . J. Biol. Chem. . 275 . 14 . 10196–201 . 2000 . 10744704 . 10.1074/jbc.275.14.10196 . etal. free.
• Dirac-Svejstrup AB, Shorter J, Waters MG, Warren G . Phosphorylation of the vesicle-tethering protein p115 by a casein kinase II-like enzyme is required for Golgi reassembly from isolated mitotic fragments. . J. Cell Biol. . 150 . 3 . 475–88 . 2000 . 10931861 . 10.1083/jcb.150.3.475 . 2175190.
• Alvarez C, Garcia-Mata R, Hauri HP, Sztul E . The p115-interactive proteins GM130 and giantin participate in endoplasmic reticulum-Golgi traffic. . J. Biol. Chem. . 276 . 4 . 2693–700 . 2001 . 11035033 . 10.1074/jbc.M007957200 . free.
• Sohda M, Misumi Y, Yamamoto A . Identification and characterization of a novel Golgi protein, GCP60, that interacts with the integral membrane protein giantin. . J. Biol. Chem. . 276 . 48 . 45298–306 . 2002 . 11590181 . 10.1074/jbc.M108961200 . etal. free.
• Shorter J, Beard MB, Seemann J . Sequential tethering of Golgins and catalysis of SNAREpin assembly by the vesicle-tethering protein p115. . J. Cell Biol. . 157 . 1 . 45–62 . 2002 . 11927603 . 10.1083/jcb.200112127 . 2173270 . etal.
• Gillingham AK, Pfeifer AC, Munro S . CASP, the alternatively spliced product of the gene encoding the CCAAT-displacement protein transcription factor, is a Golgi membrane protein related to giantin. . Mol. Biol. Cell . 13 . 11 . 3761–74 . 2003 . 12429822 . 10.1091/mbc.E02-06-0349 . 133590.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free.
• Anderson NL, Polanski M, Pieper R . The human plasma proteome: a nonredundant list developed by combination of four separate sources. . Mol. Cell. Proteomics . 3 . 4 . 311–26 . 2004 . 14718574 . 10.1074/mcp.M300127-MCP200 . etal. free.
• Colland F, Jacq X, Trouplin V . Functional proteomics mapping of a human signaling pathway. . Genome Res. . 14 . 7 . 1324–32 . 2004 . 15231748 . 10.1101/gr.2334104 . 442148 . etal.
• Breuza L, Halbeisen R, Jenö P . Proteomics of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membranes from brefeldin A-treated HepG2 cells identifies ERGIC-32, a new cycling protein that interacts with human Erv46. . J. Biol. Chem. . 279 . 45 . 47242–53 . 2004 . 15308636 . 10.1074/jbc.M406644200 . etal. free.
• Malsam J, Satoh A, Pelletier L, Warren G . Golgin tethers define subpopulations of COPI vesicles. . Science . 307 . 5712 . 1095–8 . 2005 . 15718469 . 10.1126/science.1108061 . 2005Sci...307.1095M . 12601850.
• Stelzl U, Worm U, Lalowski M . A human protein-protein interaction network: a resource for annotating the proteome. . Cell . 122 . 6 . 957–68 . 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . etal. 11858/00-001M-0000-0010-8592-0 . 8235923 . free.
• Rosing M, Ossendorf E, Rak A, Barnekow A . Giantin interacts with both the small GTPase Rab6 and Rab1. . Exp. Cell Res. . 313 . 11 . 2318–25 . 2007 . 17475246 . 10.1016/j.yexcr.2007.03.031.

Notes and References

1. Linstedt AD, Hauri HP . Giantin, a novel conserved Golgi membrane protein containing a cytoplasmic domain of at least 350 kDa . Mol Biol Cell . 4 . 7 . 679–93 . Nov 1993 . 7691276 . 300978 . 10.1091/mbc.4.7.679.
2. Oka T, Ungar D, Hughson FM, Krieger M . The COG and COPI complexes interact to control the abundance of GEARs, a subset of Golgi integral membrane proteins . Mol Biol Cell . 15 . 5 . 2423–35 . Apr 2004 . 15004235 . 404034 . 10.1091/mbc.E03-09-0699.
3. Web site: Entrez Gene: GOLGB1 golgi autoantigen, golgin subfamily b, macrogolgin (with transmembrane signal), 1.
4. Lan. Yu. Zhang. Nian. Liu. Han. Xu. Jingyue. Jiang. Rulang. 2016-07-01. Golgb1 regulates protein glycosylation and is crucial for mammalian palate development. Development. en. 143. 13. 2344–2355. 10.1242/dev.134577. 0950-1991. 4958322. 27226319.
5. Katayama. Kentaro. Sasaki. Tetsu. Goto. Syo. Ogasawara. Kei. Maru. Hiromi. Suzuki. Katsushi. Suzuki. Hiroetsu. November 2011. Insertional mutation in the Golgb1 gene is associated with osteochondrodysplasia and systemic edema in the OCD rat. Bone. en. 49. 5. 1027–1036. 10.1016/j.bone.2011.08.001. 21851869.
6. Bergen. Dylan J. M.. Stevenson. Nicola L.. Skinner. Roderick E. H.. Stephens. David J.. Hammond. Christina L.. 2017-08-15. The Golgi matrix protein giantin is required for normal cilia function in zebrafish. Biology Open. en. 6. 8. 1180–1189. 10.1242/bio.025502. 2046-6390. 5576078. 28546340.
7. Stevenson. Nicola L.. Bergen. Dylan J. M.. Skinner. Roderick E. H.. Kague. Erika. Martin-Silverstone. Elizabeth. Robson Brown. Kate A.. Hammond. Chrissy L.. Stephens. David J.. 2017-12-15. Giantin-knockout models reveal a feedback loop between Golgi function and glycosyltransferase expression. Journal of Cell Science. en. 130. 24. 4132–4143. 10.1242/jcs.212308. 0021-9533. 5769581. 29093022.
8. Sohda . M . Misumi Y . Yamamoto A . Yano A . Nakamura N . Ikehara Y . Nov 2001 . Identification and characterization of a novel Golgi protein, GCP60, that interacts with the integral membrane protein giantin . J. Biol. Chem. . 276 . 48 . 45298–306 . 0021-9258 . 11590181 . 10.1074/jbc.M108961200 . free.
9. Rosing. Mechthild. Ossendorf. Edith. Rak. Alexey. Barnekow. Angelika. July 2007. Giantin interacts with both the small GTPase Rab6 and Rab1. Experimental Cell Research. en. 313. 11. 2318–2325. 10.1016/j.yexcr.2007.03.031. 17475246.
10. Brandon. Elizabeth. Gao. Yasheng. Garcia-Mata. Rafael. Alvarez. Cecilia. Sztul. Elizabeth. August 2003. Membrane targeting of p115 phosphorylation mutants and their effects on Golgi integrity and secretory traffic. European Journal of Cell Biology. en. 82. 8. 411–420. 10.1078/0171-9335-00327. 14533739.
11. Bergen. Dylan J. M.. Stevenson. Nicola L.. Skinner. Roderick E. H.. Stephens. David J.. Hammond. Christina L.. 2017-08-15. The Golgi matrix protein giantin is required for normal cilia function in zebrafish. Biology Open. en. 6. 8. 1180–1189. 10.1242/bio.025502. 2046-6390. 5576078. 28546340.
12. Asante. D.. MacCarthy-Morrogh. L.. Townley. A. K.. Weiss. M. A.. Katayama. K.. Palmer. K. J.. Suzuki. H.. Westlake. C. J.. Stephens. D. J.. 2013-11-15. A role for the Golgi matrix protein giantin in ciliogenesis through control of the localization of dynein-2. Journal of Cell Science. en. 126. 22. 5189–5197. 10.1242/jcs.131664. 0021-9533. 3828591. 24046448.
13. Stevenson. Nicola L.. Bergen. Dylan J. M.. Skinner. Roderick E. H.. Kague. Erika. Martin-Silverstone. Elizabeth. Robson Brown. Kate A.. Hammond. Chrissy L.. Stephens. David J.. 2017-12-15. Giantin-knockout models reveal a feedback loop between Golgi function and glycosyltransferase expression. Journal of Cell Science. en. 130. 24. 4132–4143. 10.1242/jcs.212308. 0021-9533. 5769581. 29093022.
14. Stevenson. Nicola L.. Bergen. Dylan J. M.. Xu. Amadeus. Wyatt. Emily. Henry. Freya. McCaughey. Janine. Vuolo. Laura. Hammond. Chrissy L.. Stephens. David J.. 2018-05-01. Regulator of calcineurin-2 is a centriolar protein with a role in cilia length control. Journal of Cell Science. en. 131. 9. jcs212258. 10.1242/jcs.212258. 0021-9533. 5992583. 29643119.