title: Identification of the C-terminal tail domain of AHF/trichohyalin as the critical site for modulation of the keratin filamentous meshwork in the keratinocyte.
abstract: BACKGROUND
  AHF/trichohyalin is a large structural protein abundant in the inner root sheath (IRS) of anagenic hair follicles, which has been thought to mediate the keratin filamentous assembly. However, its functional mechanism is largely unknown.
  
  
  OBJECTIVE
  This study aimed at the identification of the key domain in AHF for keratin association and the establishment of a plausible mechanism for the modulation of the keratin meshwork.
  
  
  METHODS
  Several keratinocyte cell lines were introduced with the full length or several mutants of AHF, together with IRS-specific keratin krt31, and the profile of the AHF granules and the cellular behaviors were carefully analyzed.
  
  
  RESULTS
  Full length of AHF formed small round granules that clearly bound to and aligned on the exogenous keratin filaments in the keratinocytes, severely affected cellular growth, mobility and shape. Intriguingly, the removal of only 6 amino acids around the C-terminal tail of AHF resulted not only in the complete loss of its keratin adherent ability but also in a dramatic enlargement of the granules.
  
  
  CONCLUSIONS
  We propose a model for cytoskeletal modulation in the IRS of anagenic hair follicles: AHF latches onto the keratin bundles by its C-terminus and rearranges the keratin meshwork by intrinsic cohesive activity for the granule formation.
authors.affiliation: Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Takase
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hirai
mesh_terms: D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism*; D005838:Genotype; D018859:Hair Follicle / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D053564:Keratins, Hair-Specific / Q000235:genetics / Q000378:metabolism*; D053530:Keratins, Type I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs; D013997:Time Factors; D014162:Transfection
chemical_list: D007381:Intermediate Filament Proteins; D053564:Keratins, Hair-Specific; D053530:Keratins, Type I; C016159:trichohyalin