Trends in Cell Biology
ReviewFinding the Golgi: Golgin Coiled-Coil Proteins Show the Way
Section snippets
The Golgi as a Trafficking Hub
Secretory and membrane proteins are synthesised in the endoplasmic reticulum (ER) from where they are collected into transport vesicles that deliver them to the early or cis side of the Golgi stack [1]. The proteins can then remain in the Golgi as residents or pass through the cisternae to the trans-Golgi network (TGN) from where they traffic on to endosomes, lysosomes, or the plasma membrane 2, 3. The route to the plasma membrane is often constitutive, but in certain cell types some proteins
Golgins as Tethers
The cytoplasmic surface of the Golgi apparatus is decorated with large coiled-coil proteins that are referred to as ‘golgins’ [9]. These proteins are ubiquitously expressed and are well conserved in evolution with at least five apparently present in the last eukaryotic common ancestor 8, 10, 11, 12. GM130, p115, and GMAP-210 localise to the cis-Golgi, the GRIP domain golgins (golgin-97, golgin-245, GCC88, and GCC185) localise to the trans-Golgi, and TMF, CASP, golgin-84, and giantin are present
Golgins as Tethers of ER-Derived Cargo
GMAP-210 is anchored at the cis-Golgi via interaction of its C-terminal GRAB (GRIP-related Arf binding) domain with Arf1 27, 28. A short region at the N terminus of GMAP-210 forms an ‘amphipathic lipid packing sensor’ or ALPS motif that associates with highly curved membranes in vitro and binds transport vesicles in vivo 27, 29. A compelling feature of the GMAP-210 model is that ArfGAP1, a protein that inactivates Arf1, also contains an ALPS motif. Therefore, it can preferentially bind to
Tethering Intra-Golgi Vesicles by Golgins
The mammalian Golgi contains numerous resident membrane proteins such as glycosylation enzymes, transporters, and SNARES, and these must remain within specific cisternae while cargoes pass through. How this occurs has been much debated, but it is now widely believed that Golgi membrane proteins are recycled to their place of residence in retrograde transport vesicles, and several golgins have been proposed to participate in intra-Golgi vesicle capture 3, 40.
Giantin, as the name implies, is a
Tethering by Golgins of the Trans-Golgi
In addition to receiving vesicles from the ER and within the stack, the Golgi also receives cargo from the endocytic system. Ideally poised to capture these vesicles is a family of golgins that are targeted to the trans-Golgi by their C-terminal GRIP domains. Of the four mammalian GRIP domain proteins, the targeting of golgin-97, golgin-245, and GCC88 is clearly dependent on interaction of their C termini with the Golgi localised GTPase Arl1, and loss of Arl1 leads to their mislocalisation in
Tethering Complexes and SNAREs
Apart from the golgins, two other classes of proteins have been proposed to contribute to the specific capture of vesicles arriving at the Golgi. These are the multisubunit tethering complexes and the SNARE proteins 7, 8.
Three types of multisubunit complexes are important for delivery of vesicles to Golgi compartments: the COG complex acts in intra-Golgi transport; the GARP I complex is active at the trans-Golgi surface; and the TRAPP complexes act at the cis-Golgi and perhaps later in the
Concluding Remarks
The case for golgins providing specificity has been considerably strengthened by the observation that particular golgins capture subsets of vesicles, allowing their classification into functionally defined groups (Figure 2, Key Figure). In addition, for at least some multisubunit complexes there is evidence that tethering is one of their key roles. It has, however, been correctly noted that in few cases have these processes been reconstituted with purified components and thus some caution
Acknowledgments
We thank Jasper Claessen for comments on the manuscript. Funding for work on golgins in the Munro lab is provided by the Medical Research Council (MRC file reference number U105178783).
References (82)
- et al.
Golgi compartmentation and identity
Curr. Opin. Cell Biol.
(2014) Vesicular transport earns a Nobel
Trends Cell Biol.
(2014)- et al.
Tethering the assembly of SNARE complexes
Trends Cell Biol.
(2014) Unique and shared features of Golgi complex autoantigens
Autoimmun. Rev.
(2005)Structural organization of the Golgi apparatus
Curr. Opin. Cell Biol.
(2011)Testosterone deficiency accompanied by testicular and epididymal abnormalities in TMF–/– mice
Mol. Cell. Endocrinol.
(2013)Insertional mutation in the Golgb1 gene is associated with osteochondrodysplasia and systemic edema in the OCD rat
Bone
(2011)GM130 is required for compartmental organization of dendritic golgi outposts
Curr. Biol.
(2014)Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans-Golgi network
Dev. Cell
(2007)GRASP65, a protein involved in the stacking of Golgi cisternae
Cell
(1997)
The vesicle docking protein p115 binds GM130, a cis-Golgi matrix protein, in a mitotically regulated manner
Cell
Structural and functional analysis of the globular head domain of p115 provides insight into membrane tethering
J. Mol. Biol.
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.
Golgi recruitment of GRIP domain proteins by Arf-like GTPase 1 is regulated by Arf-like GTPase 3
Curr. Biol.
The ARF-like GTPases Arl1p and Arl3p act in a pathway that interacts with vesicle-tethering factors at the Golgi apparatus
Curr. Biol.
Rab and Arl GTPase family members cooperate in the localization of the golgin GCC185
Cell
The localization of the Golgin GCC185 is independent of Rab6A/A′ and Arl1
Cell
TGN golgins, Rabs and cytoskeleton: regulating the Golgi trafficking highways
Trends Cell Biol.
Congenital disorders of glycosylation: a concise chart of glycocalyx dysfunction
Trends Biochem. Sci.
Transport according to GARP: receiving retrograde cargo at the trans-Golgi network
Trends Cell Biol.
Toward a comprehensive map of the effectors of rab GTPases
Dev. Cell
The Sec34/35 Golgi transport complex is related to the exocyst, defining a family of complexes involved in multiple steps of membrane traffic
Dev. Cell
Rab GEFs and GAPs
Curr. Opin. Cell Biol.
Long coiled-coil proteins and membrane traffic
Biochim. Biophys. Acta
Golgi tethering factors
Biochim. Biophys. Acta
Golgins in the structure and dynamics of the Golgi apparatus
Curr. Opin. Cell Biol.
Uso1 protein is a dimer with two globular heads and a long coiled-coil tail
J. Struct. Biol.
Two Rab2 interactors regulate dense-core vesicle maturation
Neuron
Organization of the ER–Golgi interface for membrane traffic control
Nat. Rev. Mol. Cell. Biol.
Models for Golgi traffic: a critical assessment
Cold Spring Harb. Perspect. Biol.
Forty years of clathrin-coated vesicles
Traffic
A Nobel Prize for membrane traffic: vesicles find their journey's end
J. Cell Biol.
Tethering factors as organizers of intracellular vesicular traffic
Annu. Rev. Cell Dev. Biol.
The golgin coiled-coil proteins of the Golgi apparatus
Cold Spring Harb. Perspect. Biol.
The golgin family of coiled-coil tethering proteins
Front. Cell Dev. Biol.
Vesicles on strings: morphological evidence for processive transport within the Golgi stack
Proc. Natl. Acad. Sci. U.S.A.
Isolation of a matrix that binds medial Golgi enzymes
J. Cell Biol.
Cytoarchitecture of size-excluding compartments in living cells
J. Cell Sci.
Golgin-84 is a rab1 binding partner involved in Golgi structure
Traffic
Golgi coiled-coil proteins contain multiple binding sites for Rab family G proteins
J. Cell Biol.
Multiple Rab GTPase binding sites in GCC185 suggest a model for vesicle tethering at the trans-Golgi
Mol. Biol. Cell
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