title: Epsin 3 is a novel extracellular matrix-induced transcript specific to wounded epithelia.
abstract: Using an in vitro model of keratinocyte activation by the extracellular matrix following injury, we have identified epsin 3, a novel protein closely related to, but distinct from previously described epsins. Epsin 3 contains a domain structure common to this gene family, yet demonstrates novel differences in its regulation and pattern of expression. Epsin 3 mRNA and protein were undetectable in keratinocytes isolated from unwounded skin, but induced in cells following contact with fibrillar type I collagen. The native triple helical structure of collagen was required to mediate this response as cells failed to express epsin 3 when plated on gelatin. Consistent with the reported function of other epsins, epsin 3 was evident in keratinocytes as punctate vesicles throughout the cytoplasm that partially co-localized with clathrin. In addition, epsin 3 exhibited nuclear accumulation when nuclear export was inhibited. In contrast to other known epsins, epsin 3 was restricted to keratinocytes migrating across collagen and down-regulated following cell differentiation, suggesting that expression was spatially and temporally regulated. Indeed, epsin 3 was localized specifically to migrating keratinocytes in cutaneous wounds, but not found in intact skin. Intriguingly, Northern hybridization and reverse transcriptase-polymerase chain reaction experiments indicated that epsin 3 expression was restricted to epithelial wounds or pathologies exhibiting altered cell-extracellular matrix interactions. Thus, we have identified a novel type I collagen-induced epsin that demonstrates structural and behavioral similarity to this gene family, yet exhibits restricted and regulated expression, suggesting that epsin 3 may serve an important function in activated epithelial cells during tissue morphogenesis.
authors.affiliation: Department of Cell Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Spradling
authors.forename: A E
authors.initials: AE
authors.lastname: McDaniel
authors.forename: J
authors.initials: J
authors.lastname: Lohi
authors.forename: B K
authors.initials: BK
authors.lastname: Pilcher
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D005091:Exons; D005109:Extracellular Matrix / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry; D009928:Organ Specificity; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012879:Skin Physiological Phenomena; D014158:Transcription, Genetic; D033921:Vesicular Transport Proteins; D014947:Wounds and Injuries / Q000235:genetics / Q000503:physiopathology*; D014981:Xenopus
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C434483:EPN3 protein, human; D009479:Neuropeptides; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; C114154:epsin; D003094:Collagen