PUBLICATION

The ENTH domain protein Clint1 is required for epidermal homeostasis in zebrafish

Authors
Dodd, M.E., Hatzold, J., Mathias, J.R., Walters, K.B., Bennin, D.A., Rhodes, J., Kanki, J.P., Look, A.T., Hammerschmidt, M., and Huttenlocher, A.
ID
ZDB-PUB-090706-18
Date
2009
Source
Development (Cambridge, England)   136(15): 2591-2600 (Journal)
Registered Authors
Dodd, M. Ernest, Hammerschmidt, Matthias, Hatzold, Julia, Huttenlocher, Anna, Kanki, John, Look, A. Thomas, Mathias, Jonathan, Rhodes, Jennifer, Walters, Kevin
Keywords
Epidermis, Zebrafish, Inflammation, Hemidesmosome
MeSH Terms
  • Desmosomes/metabolism
  • Desmosomes/ultrastructure
  • Zebrafish Proteins/chemistry*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Epithelium/metabolism
  • Epithelium/ultrastructure
  • Mutagenesis, Insertional
  • Protein Transport
  • Inflammation/pathology
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Cell Proliferation
  • Animals
  • beta Karyopherins/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Leukocytes/cytology
  • Leukocytes/metabolism
  • Phenotype
  • Transport Vesicles/metabolism
  • Transport Vesicles/ultrastructure
  • Epidermis/metabolism*
  • Epidermis/pathology
  • Epidermis/ultrastructure
  • Cell Death
  • Mesoderm/metabolism
  • Mesoderm/ultrastructure
  • Protein Structure, Tertiary
  • Gene Expression Regulation, Developmental
  • Phagocytosis
  • Homeostasis*
  • Mutation/genetics
(all 34)
PubMed
19570844 Full text @ Development
Abstract
Epidermal hyperproliferation and inflammation are hallmarks of the human condition psoriasis. Here, we report that a zebrafish line with a mutation in the cargo adaptor protein Clint1 exhibits psoriasis-like phenotypes including epithelial hyperproliferation and leukocyte infiltration. Clint1 is an ENTH domain-containing protein that binds SNARE proteins and functions in vesicle trafficking; however, its in vivo function in animal models has not been reported to date. The clint1 mutants exhibit chronic inflammation characterized by increased Interleukin 1beta expression, leukocyte infiltration, bidirectional trafficking and phagocytosis of cellular debris. The defects in clint1 mutants can be rescued by expression of zebrafish clint1 and can be phenocopied with clint1-specific morpholinos, supporting an essential role for Clint1 in epidermal development. Interaction studies suggest that Clint1 and Lethal giant larvae 2 function synergistically to regulate epidermal homeostasis. Accordingly, clint1 mutants show impaired hemidesmosome formation, loss of cell-cell contacts and increased motility suggestive of epithelial to mesenchymal transition. Taken together, our findings describe a novel function for the ENTH domain protein Clint1 in epidermal development and inflammation and suggest that its deficiency in zebrafish generates a phenotype that resembles the human condition psoriasis.
Genes / Markers
Figures
Figure Gallery (14 images) / 2
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
AB + MO1-llgl2 + MO2-clint1astandard conditionsLong-pec
AB + MO1-llgl2 + MO2-clint1astandard conditionsLong-pec
AB + MO2-clint1astandard conditionsPrim-25
AB + MO2-clint1astandard conditionsPrim-25
AB + MO2-clint1astandard conditionsPrim-25
clint1ahi1520Tg/hi1520Tg (AB)standard conditionsPrim-25
clint1ahi1520Tg/hi1520Tg (AB)standard conditionsPrim-25
clint1ahi1520Tg/hi1520Tg (AB)standard conditionsPrim-25
clint1ahi1520Tg/hi1520Tg (AB)standard conditionsLong-pec
clint1ahi1520Tg/hi1520Tg (AB)standard conditionsLong-pec
1 - 10 of 24
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hi1520TgTransgenic Insertion
uwm1TgTransgenic Insertion
    vu119TgTransgenic Insertion
      1 - 3 of 3
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      clint1aMO1-clint1aMRPHLNO
      clint1aMO2-clint1aMRPHLNO
      llgl2MO1-llgl2MRPHLNO
      vti1bMO1-vti1bMRPHLNO
      vti1bMO2-vti1bMRPHLNO
      1 - 5 of 5
      Show
      Fish
      Fish
      AB
      AB + MO1-llgl2
      AB + MO1-llgl2 + MO2-clint1a
      AB + MO2-clint1a
      clint1ahi1520Tg/hi1520Tg (AB)
      clint1ahi1520Tg/hi1520Tg; uwm1Tg (AB)
      clint1ahi1520Tg/+ (AB)
      uwm1Tg (AB)
      vu119Tg (AB)
      vu119Tg + MO2-clint1a (AB)
      1 - 10 of 10
      Show
      Antibodies
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      GFPEFGGFP
      1 - 2 of 2
      Show
      Mapping
      No data available
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      Citation
      Dodd, M.E., Hatzold, J., Mathias, J.R., Walters, K.B., Bennin, D.A., Rhodes, J., Kanki, J.P., Look, A.T., Hammerschmidt, M., and Huttenlocher, A. (2009) The ENTH domain protein Clint1 is required for epidermal homeostasis in zebrafish. Development (Cambridge, England). 136(15):2591-2600.