The Golgin Coiled-Coil Proteins of the Golgi Apparatus
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Downloaded from http://cshperspectives.cshlp.org/ on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press The Golgin Coiled-Coil Proteins of the Golgi Apparatus Sean Munro MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom Correspondence: [email protected] A number of long coiled-coil proteins are present on the Golgi. Often referred to as “golgins,” they are well conserved in evolution and at least five are likely to have been present in the last common ancestor of all eukaryotes. Individual golgins are found in different parts of the Golgi stack, and they are typically anchored to the membrane at their carboxyl termini by a transmembrane domain or by binding a small GTPase. They appear to have roles in mem- brane traffic and Golgi structure, but their precise function is in most cases unclear. Many have binding sites for Rab family GTPases along their length, and this has led to the sugges- tion that the golgins act collectively to form a tentacular matrix that surrounds the Golgi to capture Rab-coated membranes in the vicinity of the stack. Such a collective role might explain the lack of cell lethality seen following loss of some of the genes in human familial conditions or mouse models. oiled-coils are widely occurring protein of the protein is predicted to form a coiled-coil, Cstructural motifs in which two or more and that their carboxyl termini mediate attach- a-helices wind around each other to form an ment to Golgi membranes. They are generally extended rod-like structure. Proteins contain- ubiquitously expressed and well conserved in ing such structures are found in many parts of evolution, but their coiled-coil regions are rela- the cell, and play diverse roles including organ- tively poorly conserved suggesting that much of izing centrosomes, chromatin, and synapses, or their length serves as spacer. Given that 500 res- serving as molecular motors. As such there idues of coiled-coil is 75 nm in length then may seem little reason to consider them col- the proteins could extend for 100–400 nm. lectively beyond an interest in the structural Some of the proteins have regions which appear and biophysical properties of the coiled-coil likely to be unstructured and hence could serve itself. However, the Golgi is unique amongst as extensions or hinges to increase the proteins’ the cellular compartments in that several differ- reach and flexibility (Oas and Endow 1994; ent large coiled-coil proteins are present on its Yamakawa et al. 1996). These shared features cytoplasmic surface (Gillingham and Munro suggest that the proteins serve related functions 2003; Lupashin and Sztul 2005; Short et al. on the Golgi. The term “golgin” is often applied 2005; Ramirez and Lowe 2009). A number of to these proteins having been coined in early these share a similar organization in that most studies when several were found as human Editors: Graham Warren and James Rothman Additional Perspectives on The Golgi available at www.cshperspectives.org Copyright # 2011 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a005256 Cite this article as Cold Spring Harb Perspect Biol 2011;3:a005256 1 Downloaded from http://cshperspectives.cshlp.org/ on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press S. Munro autoantigens (Fritzler et al. 1993), but the term how their properties might reflect a shared lacks a clear definition. Toprovide a focus to this function in Golgi organization and traffic. article, I will concentrate on “golgins” as defined by being a protein that is found primarily, if not exclusively, on the Golgi and is predicted GOLGINS AT THE CIS-GOLGI: GM130, to form a homodimeric parallel coiled-coil GMAP-210, AND GOLGIN-160 over most of its length. Proteins with shorter regions of coiled-coil are more likely to have GM130 and its Relatives roles distinct to the golgins, especially if further Identified as a Golgi autoantigen, GM130 is a domains are present. ubiquitously expressed protein of the cis-Golgi Golgin coiled-coil proteins are found on (Fritzler et al. 1993; Nakamura et al. 1995). the cis-face of the Golgi, around the rims of The carboxyl terminus of the rat protein has the stack and on the trans-face of the Golgi been shown to bind the lipid-anchored PDZ (Fig. 1). The human golgins are summarized domain protein GRASP65, and this region of in Table 1, along with their orthologs in model the protein is required for Golgi localization organisms and the rather confusing gene names (Barr et al. 1997; Barr et al. 1998). The protein inflicted by the Human Gene Nomenclature is conserved in metazoans and fungi, and a Committee. I discuss what is known about the diminutive yeast ortholog, Bug1, binds to the individual proteins from each of the parts of yeast ortholog of GRASP65 (Behnia et al. the Golgi, and mention briefly the Golgi 2007). However the protein does not appear coiled-coil proteinsthat are probably not golgins. to have orthologs outside of opisthikonts, in I then discuss how the golgins are regulated and contrast to GRASP65 which is conserved in cis Golgi GM130 GMAP-210 Golgin-160 Golgi rims Giantin Golgin-84 CASP trans Golgi Golgin-245 GCC185 Golgin-97 GCC88 TMF1 Predicted coiled-coil TMD 500 aa GRIP GRAB ALPS Figure 1. The golgin coiled-coil proteins of humans. Schematic representations of known human golgins. Regions predicted to form coiled-coils are shown in gray, and known domains involved in protein function or subcellular targeting are indicated. 2 Cite this article as Cold Spring Harb Perspect Biol 2011;3:a005256 Downloaded from http://cshperspectives.cshlp.org/ on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press The Golgin Coiled-Coil Proteins Table 1. The canonical golgins of the human Golgi and their orthologs. Protein Alternative Human gene D. melanogaster C. elegans S. cerevisiae A. thaliana names symbol GM130 golgin-95 GOLGA2 CG11061 F33G12.5 BUG1 GMAP-210 Trip230 TRIP11 CG7821 Y111B2A.4 RUD3 At3g6157 CEV14 At2g46180 golgin-160 Mea-2 GOLGA3 IIGP165 GCP170 golgin-84 RFG5 GOLGA5 CG17785 T24B1.1 At1g18190 At2g19950 CASP CUX1 (alt) Y54F10AM.4c COY1 At3g18480 (ceh-44) giantin macrogolgin GOLGB1 CG6450 GCP372 (lva) golgin-97 GOLGA1 CG4840 IMH1 At5g66030 (cbs) golgin-245 p230 GOLGA4 CG3493 F59A2.2/6 tGolgin-1 GCC88 GCC1 CG10703 C15C7.2.1 (klp-8) GCC185 GCC2 CG3532 T05G5.9 TMF ARA160 TMF1 CG4557 F39H12.1 SGM1 At1g79830 protozoa, and has been reported to have roles in temperature sensitive, it shows no defects in Golgi structure and the traffic of specific cargo Golgi structure or protein transport at the beyond binding GM130 (D’Angelo et al. 2009; permissive temperature (Vasile et al. 2003). Xiang and Wang 2010). GM130 is also the Golgi binding site of a protein GM130 has been shown to interact via its kinase linked to directed cell migration, and is amino terminus with p115, a cytosolic protein also suggested to have roles in SNARE assembly that is comprised of armadillo repeats followed and regulation of centrosomes (reviewed in by a region of coiled-coil, and which has been Nakamura 2010). shown to be involved in tethering ER-derived In addition to GM130, the human genome transport vesicles to the Golgi in mammals contains a family of over 30 genes that are and yeast (Sapperstein et al. 1995; Nakamura related to GM130 and are referred to as GOL- et al. 1997; Cao et al. 1998; Satoh and Warren GA6A-J, GOLGA6AL1-10, and GOLGA8A-J 2008; An et al. 2009; Striegl et al. 2010). (Jiang et al. 2008). Most are present in the re- GM130 is also an effector for the small GTPases peats of an element that derived from GOLGA2, Rab1, Rab30, and Rab33b (Moyer et al. 2001; the gene encoding GM130 on chromosome 9, Valsdottir et al. 2001; Weide et al. 2001; Sinka but has duplicated on the long arm of chromo- et al. 2008). However, it seems unlikely that some 15. These repeats appear to have been GM130 is essential for membrane traffic as a generated by genome rearrangements during mutant Chinese hamster cell line has been iden- primate evolution as similar repeats are found tified that lacks detectable GM130 and although in the genome of the macaque, an old-world Cite this article as Cold Spring Harb Perspect Biol 2011;3:a005256 3 Downloaded from http://cshperspectives.cshlp.org/ on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press S. Munro monkey, whereas nonprimate vertebrates such of GMAP-210 causes IFT20 to be displaced as mice only have the GOLGA2 gene (Zody from the Golgi (Follit et al. 2008). et al. 2006). These genes are unlikely to all be A null mutant in mouse GMAP-210 results pseudogenes as they are predicted to encode in impaired skeletal development, and loss-of- proteins and are well represented in EST function mutations in the human gene have databases. They are generally internally deleted been found to underlie some cases of familial versions of GM130 and one, golgin-67 (GOL- skeletal dysplasia (Smits et al. 2010). In the GA8A), has been shown to be widely expressed mutant mice there is a defect in secretion of and present on the Golgi (Eystathioy et al. 2000; extracellular matrix by chondrocytes, and Golgi Jakymiw et al. 2000). Their significance is structure appears perturbed, but effects on cilia unclear, and may be difficult to address, but at are disputed (Follit et al. 2008; Smits et al. the very least, they are relevant to the study of 2010). Genetic studies in Drosophila and yeast GM130 function in primate cell lines.