New facets of keratin K77: interspecies variations of expression and different intracellular location in embryonic and adult skin of humans and mice.
The differential expression of keratins is central to the formation of various epithelia and their appendages. Structurally, the type II keratin K77 is closely related to K1, the prototypical type II keratin of the suprabasal epidermis. Here, we perform a developmental study on K77 expression in human and murine skin. In both species, K77 is expressed in the suprabasal fetal epidermis. While K77 appears after K1 in the human epidermis, the opposite is true for the murine tissue. This species-specific pattern of expression is also found in conventional and organotypic cultures of human and murine keratinocytes. Ultrastructure investigation shows that, in contrast to K77 intermediate filaments of mice, those of the human ortholog are not attached to desmosomes. After birth, K77 disappears without deleterious consequences from human epidermis while it is maintained in the adult mouse epidermis, where its presence has so far gone unnoticed. After targeted Krt1 gene deletion in mice, K77 is normally expressed but fails to functionally replace K1. Besides the epidermis, both human and mouse K77 are present in luminal duct cells of eccrine sweat glands. The demonstration of a K77 ortholog in platypus but not in non-mammalian vertebrates identifies K77 as an evolutionarily ancient component of the mammalian integument that has evolved different patterns of intracellular distribution and adult tissue expression in primates.
Genetics of Skin Carcinogenesis, A110, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany, langbein@dkfz.de.
Lutz
L
Langbein
Julia
J
Reichelt
Leopold
L
Eckhart
Silke
S
Praetzel-Wunder
Walter
W
Kittstein
Nikolaus
N
Gassler
Juergen
J
Schweizer
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry / Q000196:embryology / Q000378:metabolism; D006071:Gorilla gorilla; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D007633:Keratins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000737:chemistry / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism
D012333:RNA, Messenger; D007633:Keratins