BUXTON, RS

COWIN, P

FRANKE, WW

GARROD, DR

GREEN, KJ

KING, IA

KOCH, PJ

MAGEE, AI

REES, DA

STANLEY, J

STEINBERG, MS

The Journal of Cell Biology

Spiral - Imperial College Digital Repository

Mini-Review Nomenclature of the Desmosomal Cadherins R.  S. Bux ton ,*  P. C o w i n , t  W. W. Franke ,§  D. R .  Garrod,II  K .  J. Green,1  I .  A.  King ,*  P. J. Koch,§  A. I. Magee,* D. A. Rees,* J. R. Stanley,** a n d  M. S. Steinberg~§ * Laboratory of Eukaryotic Molecular Genetics, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom; ~New York University Medical Center, School of Medicine, New York University, New York 10016; §Institut fiir Zell- und Tumorbiologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Postfach 10 19 49, D-6900 Heidelberg 1, Germany; II Department of Biological Sciences, Stopford Building, University of Manchester, Manchester M13 9PT, United Kingdom; I Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611-3008; ~Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; and §§Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014 T n~ results of recent cDNA cloning and sequencing have established that the major glycoproteins of the desmosome type of cell-cell junctions are members of the cadherin family of cell adhesion molecules (Goodwin et al., 1990; Holton et al., 1990; Koch et al., 1990, 1991b; Collins et al., 1991; Mechanic et al., 1991; Nilles et al., 1991; Parker et al., 1991; Wheeler et al., 1991; and for reviews see Schwarz et al., 1990; Magee and Buxton, 1991; Legan et al., 1992). The fundamental structure of the "classi- cal" cadherins, such as E-cadherin (uvomorulin), P-cadherin, and N-cadherin, consists of an extracellular domain, which contains four major repeats and includes sequences involved in Ca2÷-binding, a transmembrane domain and a cytoplas- mic domain. Two types of desmosomal cadherin have been described, the desmocollins and the desmogleins. The name 'desmoglein' was originally coined to refer to all desmosomal glycoproteins (Gorbsky and Steinberg, 1981). However, Cowin et al. (1984) introduced the term 'desmocol- lin' to distinguish two types of desmosomal glycoproteins that seemed to have different properties. In fact, the homol- ogy between them is no greater than the homology between the desmosomal and classical cadherins. The desmocollins display a higher degree of homology with the classical cad- herins, whereas the desmogleins are distinguished in having an extra carboxy-terminal domain containing a number of repeats of a 29 -1- 1 residue sequence not present in the other cadherins nor as yet found in other proteins. There are experimental observations indicative of an in- volvement in cell-cell adhesion in the case of a desmocollin and two desmogleins. In the former, this is because Fab' frag- ments of polyclonal anti-desmocollin antibodies inhibited the formation of antibody-stainable desmosomal plaques in MDBK cells (Cowin et al., 1984). In the case of a des- moglein, the autoantigen in the blistering skin disease pem- phigus vulgaris (PV), PV IgG alone, without complement or inflammatory cells, can cause loss of cell-cell adhesion in skin organ culture, with the same histology as seen in PV blisters (Schiltz and Michel, 1976; Hashimoto et al., 1983). Similarly, Fab' fragments from endemic pemphigus foliaceus autoantibodies (desmoglein DGI) cause loss of cell adhesion in neonatal mice (Rock et al., 1990). The desmosomal cad- herins appear to be confined to the desmosome type of cell junction, although in the case of one desmoglein, the PV antigen, published results are inconclusive, with some indi- cating distribution also on the extra-desmosomal cell mem- brane (Wolff and Schreiner, 1971; Jones et al., 1986). More recent studies show a predominately desmosomal localiza- tion (Karpati, S., M. Amagal, K. Cehrs, V. Klaus-Kovtun, and J. R. Stanley. 1992. J. Invest. Dermatol. 98: 580a; and for review see Stanley, 1992). For some time it has been known that certain anti-desmo- collin (Parrish et al., 1986) and anti-desmoglein (Jones et al., 1987) antibodies only recognize desmosomes in epi- dermal suprabasal cells, suggesting variations in the compo- sition of these junctions. While it was possible that these results were due to differential masking of epitopes, it did suggest that there could be variation in the composition of these junctions. In the case of the desmocollins, amino acid sequencing of proteolytic products suggested that there were different isoforms of the desmocollins which were expressed in different locations in human epidermis (King et al., 1991). Moreover, the first published sequences of desmocollins from bovine snout epithelium (Collins et al., 1991; Koch et al., 1991b; Mechanic et al., 1991) and from human keratino- cytes (Parker et al., 1991) showed only 50% identity of their deduced amino acid sequences. Species homologues of other cadherin subtypes show substantially greater identity than this, so the possibility existed that these desmocollins were not species homologues but represented different subfamilies. This has now been confirmed for two bovine desmocollins, termed desmocollin type 1 and type 2 (Koch et al., 1992). In the case of the desmogleins, determinations of amino acid sequences derived from human cDNA clones encoding des- moglein from different kinds of cells (Koch et al., 1991a) or selected using autoantibodies from the blistering skin disease pemphigis vulgaris (Amagai et al., 1991) have also revealed the existence of cell type-specific isoforms for these proteins distinct from the originally described human desmoglein (Wheeler et al., 1991; Nilles et al., 1991; for review see Bux- ton and Magee, 1992). The nomenclature of the desmosomal glycoproteins was discussed at a Ciba Foundation symposium held in 1986 © The Rockefeller University Press, 0021-9525/93/05/481/3 $2.00 The Journal of Cell Biology, Volume 121, Number 3, May 1993 481-483 481 Table L Gene and Protein Names of the Desmosomal Cadherins Gene name Human chromosomal assignment (abbreviation) Proteins Human synonyms Bovine equivalent (and reference) Desmocollins DSCI*** Dsc la  DGIV* band 4a* 1 Type 1 desmocollin,~ 18~§ Dsc lb  DGV* band 4b* ] desmoglein IIll Dsc2a ~10 ] Type 2 desmocollin~ Dsc2b J Dsc3a DGII ] Type 3 desmocoUinllllll Dsc3b DGIII ] DSC2 DSC3*** 9pllll Desmogleins (defined by the presence of  the 29 + 1 residue cytoplasmic repeat) DSG1 Dsgl  DGI band 3,~ desmoglein 111 150-165K¶ DSG2 Dsg2 HDGC** DSG3 Dsg3 PVA** 181111 187¶ 18"** * Buxton and Magee, 1991; King, I. A., unpublished data; Theis et al., 1993. Skerrow and Matoltsy, 1974; Kapprell et al., 1985. Koch et al., 1992. II Giudice et al., 1984. ¶ Cowin and Garrod, 1983. ** Koch et al., 1991a. ~ Amagai et al., 1991. §J J. Aroemann, unpublished data. IlU Arnemann et ai., 1991. ¶¶ Arnemann et al., 1992b. *** Arnemann et al., 1992a. 1:~; The genes to which DSC1 and DSC3 refer are changed from DSC2 and DSC1, respectively, described in Buxton and Magee (1991), so as to fit in with the nomenclature proposed in the present paper. H~ No human equivalent to the bovine type 2 desmocoUin has yet been described. IIIIII Legan, P. R., K. K. M. Yue, and D. R. Garrod, unpublished data; Garrod, 1993; Troyanovsky et al., 1993. (Bock and Clark, 1987), but unfortunately none of the schemes suggested then is able to embrace the diversity of the different desmosomal cadherin isoforms, the number of which will probably increase. We therefore propose a new nomenclature for the desmocollins and desmogleins (Table I). This is based on the accepted gene symbols which have been approved by the Human Gene Nomenclature Commit- tee. For the desmocollin genes this is DSC and for the des- moglein genes it is DSG. To date reports have been published of the human chromo- somal assignments of three desmoglein genes, viz. DSG1, DSG2, and DSG3 (Arnemann et al., 1991, 1992a,b). It is proposed therefore that their protein products be named des- moglein 1, 2, and 3 and abbreviated Dsgl, Dsg2, Dsg3, re- spectively. Dsg3, the pemphigus vulgaris antigen, is included in the desmogleins by virtue of its longer cytoplasmic do- main, including the presence of two repeats of the 29 + 1 residue motif, although the fifth extracellular domain is more like the classic cadherins and the desmocoUins than the desmogleins. In the case of the desmocollins, the assignment of one hu- man gene DSC has been reported (Arnemarm et al., 1991). It has been proposed that this gene be termed DSC3, since it codes for the human orthologue of the bovine desmocollin type 3 (Dsc3) (Legan, P. R., K. K. M. Yue, and D. R. Gar- rod, unpublished data; Garrod, 1993; see also Troyanovsky et al., 1993) and that the type 1 desmocollin gene and protein be DSC1 and Dscl, respectively. No human equivalent of bo- vine type 2 desmocollin (Koch et al., 1992) has yet been de- scribed. The desmoeollin genes each code for two products differing by ,,o6 kD, derived from alternatively spliced tran- scripts from single genes. This results in the inclusion of a 46-bp exon containing an in-frame stop codon in the mRNA encoding the smaller form (Collins et al., 1991; Parker et al., 1991). It is proposed that the larger alternatively spliced pro- tein product of each gene should be designated the 'a' form and the smaller the 'b' form. The six desmocollin proteins recognized so far are therefore referred to as la, lb, 2a, 2b, 3a, and 3b. The probable relationships of the bovine and hu- man desmosomal cadherin proteins are indicated in Table I. This simple type of nomenclature, which is independent of tissue distribution of the proteins, can easily be extended as new genes are discovered and could also encompass other desmosomal proteins such as the desmoplakins, or indeed other junctional or cytoskeletal proteins where a plethora of isoforms renders it difficult to distinguish between types. It will also enable easy comparison between different or- ganisms. Received f~r publication 5 February 1993. Refere~e$ Amagai, M., V. Klans-Kovton, and J. R. Stanley. 1991. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. 67:869~877. Arnemann, J., N. K. Spurr, G. N. Wheeler, A. E. Parker, and R. S. Buxton. 1991. Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPm (JUP). Genomics. 10:640-645. Arnemann, J., N. K. Spurr, and R. S. Buxton. 1992a. The human gene (DSG3) coding for the pemphigus vulgaris antigen is, like the genes coding for the other two known desmogleins, assigned to chromosome 18. Hum. Genet. 89:347-350. Arnemann, J., N. K. Spun, A. I. Magee, and R. S. Buxton. 1992b. The human The Journal of Cell Biology, Volume 121, 1993 482 gene (DSG2) coding for HDGC, a second member of the desmoglein sub- family of the desmosomal cadherins, is, like DSG1 coding for desmoglein DGI, assigned to chromosome 18. C-enomics. 13:484--486. Bock, G., and S. Clark. 1987. Junctional complexes of epithelial cells. Ciba Found. Symp. 125. Buxton, R. S., and A. I. Magee. 1992. Structure and interactions of des- mosomal and other cadherins. Semin. Cell Biol. 3:157-167. Collins, J. E., P. K. Legan, T. P. Kenny, J. MacGarvie, J. L. Holton, and D. R. Garrod. 1991. Cloning and sequence analysis of desmosomal glyco- protein 2 and glycoprotein 3 (desmocollins): cadherin-like desmosomal ad- hesion molecules with heterogeneous cytoplasmic domains. J. Cell Biol. 113:381-391. Cowin, P., and D. R. Garrod. 1983. Antibodies to epithelial desmosomes show wide tissue and species cross-reactivity. Nature (Lond.). 302:148-150. Cowin, P., D. Mattey, and D. Garrod. 1984. Identification of desmosomal sur- face components (desmocollins) and inhibition of desmosome formation by specific Fab'. J. Cell Sci. 70:41-60. Garrod, D. R. 1993. Desmosomes and bemidesmosomes. Curr. Opin. Cell Biol. 5:30-40. Giudice, G. J., S. M. Cohen, N. H. Patel, andM. S. Steinberg. 1984. Immuno- logical comparison of desmosomal components from several bovine tissues. J. Cell Biochem. 26:35--45. Goodwin, L., J. E. Hill, K. Raynor, L. Raszi, M. Manabe, and P. Cowin. 1990. 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Complete amino acid sequence oftbe epidermal desmoglein precursor polypeptide and identification of a second type ofdesmoglein gene. Eur. J. Cell Biol. 55:200-208. Koch, P. J., M. D. Goldschmidt, M. J. Walsh, R. Zimbelmann, M. Schmelz, and W. W. Franke. 1991b. Amino acid sequence of bovine muzzle epithelial desmocollin derived from cloned eDNA: a novel subtype of desmosomal cadherins. Differentiation. 47:29-36. Koch, P. J., M. D. Goldschmidt, R. Zimbelmann, R. Troyanovsky, and W. W. Franke. 1992. Complexity and expression patterns of the desmosomal cadhe- rins. Proc. Natl. Acad. Sci. USA. 89:353-357. Legan, P. K., J. E. Collins, and D. R. Garrod. 1992. The molecular biology of desmosomes and hemidesmosomes: 'What's in a name?'. Bioessays. 14:385-393. Magee, A. I., and R. S. Buxtnn. 1991. Transmembrane molecular assemblies regulated by the greater cadherin family. Curt. Opin. CellBiol. 3:854-861. Mechanic, S., K. Raynor, J. E. Hill, and P. Cowin. 1991. 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NOMENCLATURE OF THE DESMOSOMAL CADHERINS

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NOMENCLATURE OF THE DESMOSOMAL CADHERINS

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