Finding the Golgi: Golgin Coiled-Coil Proteins Show the Way

doi:10.1016/j.tcb.2016.02.005

Trends in Cell Biology

Volume 26, Issue 6, June 2016, Pages 399-408

https://doi.org/10.1016/j.tcb.2016.02.005 Get rights and content

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Golgins localise to specific cisternae within the Golgi stack. Recent results demonstrate that these proteins are sufficient to direct the tethering of transport vesicles when relocated to a different organelle.

Subsets of the golgins capture vesicles from different destinations within the cell. For example, GM130 and GMAP-210 bind ER-derived vesicles while three GRIP domains proteins tether vesicles arriving from endosomes.

All golgins localise to the Golgi via their C termini but the regions responsible for vesicle capture are generally unknown. One exception is GMAP-210 where an N-terminal ALPS motif is clearly important.

Multisubunit tethering complexes participate in vesicle delivery. While their precise mechanism of action is unclear, they are likely to act downstream of golgins.

The Golgi apparatus lies at the centre of the secretory pathway. It consists of a series of flattened compartments typically organised into a stack that, in mammals, is connected to additional stacks to form a Golgi ribbon. The Golgi is responsible for the maturation and modification of proteins and lipids, and receives and exports vesicles to and from multiple destinations within the cell. This complex trafficking network requires that only the correct vesicles fuse with the correct destination membrane. Recently, a group of coiled-coil proteins called golgins were shown to not only capture incoming vesicles but to also provide specificity to the tethering step. This raises many interesting questions about how they interact with other components of membrane traffic, some of which may also contribute to specificity.

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).

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Trends in Cell Biology

ReviewFinding the Golgi: Golgin Coiled-Coil Proteins Show the Way

Trends

Section snippets

The Golgi as a Trafficking Hub

Golgins as Tethers

Golgins as Tethers of ER-Derived Cargo

Tethering Intra-Golgi Vesicles by Golgins

Tethering by Golgins of the Trans-Golgi

Tethering Complexes and SNAREs

Concluding Remarks

Acknowledgments

Curr. Opin. Cell Biol.

Trends Cell Biol.

Trends Cell Biol.

Autoimmun. Rev.

Curr. Opin. Cell Biol.

Mol. Cell. Endocrinol.

Bone

Curr. Biol.

Dev. Cell

Cell

Cell

J. Mol. Biol.

J. Biol. Chem.

Curr. Biol.

Curr. Biol.

Cell

Cell

Trends Cell Biol.

Trends Biochem. Sci.

Trends Cell Biol.

Dev. Cell

Dev. Cell

Curr. Opin. Cell Biol.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Curr. Opin. Cell Biol.

J. Struct. Biol.

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

Review
Finding the Golgi: Golgin Coiled-Coil Proteins Show the Way