Differential structural properties and expression patterns suggest functional significance for multiple mouse desmoglein 1 isoforms.
The four isoforms of desmosomal cadherin desmogleins (Dsg1-4) are expressed in epithelial tissues in a differentiation-specific manner. Extensive sequencing of the human genome has revealed only one copy of the Dsg1 gene. However, we recently cloned two novel additional mouse Dsg1 genes, Dsg1-beta and -gamma, which flank the original Dsg1-alpha on chromosome 18. Sequence conservation between the Dsg1 isoforms diverged significantly at exon 11, particularly in the region that encodes for the extracellular anchoring (EA) domains. Computational analysis revealed very low hydrophilic potential of the Dsg1-gamma EA compared with the corresponding sequences of Dsg1-alpha and -beta, suggesting that the Dsg1-gamma EA domain may have a stronger affinity to the cell membrane. We generated antibodies using synthetic peptides or recombinant proteins localized within the EA domains. These antibodies were tested for their specificity and were then used to demonstrate expression of Dsg1 isoforms in various tissues. In the epidermis, all Dsg1 isoforms were differentially expressed in the differentiating cell layers. In the hair follicle, all Dsg1 isoforms were present throughout the entire process of its development and cycling but the expression of Dsg1 isoforms is subject to significant hair cycle-dependent changes. Dsg1-beta and -gamma, but not Dsg1-alpha, were detected in the sebaceous gland epithelium and the stratified epithelium of the stomach. Finally, Dsg1-alpha and Dsg1-beta, but not Dsg1-gamma, are proteolytically cleaved by exfoliative toxin A. These results suggest that the developmental complexity of mouse tissues, including skin and hair, may play a significant role in the evolutionary driving force to maintain multiple Dsg1 genes in mouse.
Brennan
Donna
D
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Hu
Ying
Y
Kljuic
Ana
A
Choi
Yoowon
Y
Joubeh
Sohaila
S
Bashkin
Marisa
M
Wahl
James
J
Fertala
Andrzej
A
Pulkkinen
Leena
L
Uitto
Jouni
J
Christiano
Angela M
AM
Panteleyev
Andrey
A
Mahoney
My G
MG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D051183:Desmoglein 1; D003896:Desmosomes / Q000378:metabolism; D047108:Embryonic Development / Q000502:physiology; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism*; D005083:Exfoliatins / Q000737:chemistry; D005091:Exons / Q000235:genetics; D018859:Hair Follicle / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012627:Sebaceous Glands / Q000166:cytology / Q000378:metabolism; D014018:Tissue Distribution / Q000276:immunology; D015854:Up-Regulation
D015820:Cadherins; D051183:Desmoglein 1; D005083:Exfoliatins; D020033:Protein Isoforms; D002118:Calcium