title: Huntingtin Supplies a csaA-Independent Function Essential for EDTA-Resistant Homotypic Cell Adhesion in Dictyostelium discoideum.
abstract: BACKGROUND
  The CAG triplet repeat expansion mutation in the HTT locus, which results in neurodegeneration in Huntington's disease, elongates a polyglutamine tract in huntingtin, a HEAT/HEAT-like protein that has been highly structurally conserved through evolution. In several organisms, huntingtin is necessary for proper cell-cell adhesion and normal development.
  
  
  OBJECTIVE
  Dictyostelium discoideum huntingtin null (htt-) cells display a variety of developmental abnormalities and completely fail to acquire EDTA-resistant homotypic cell adhesion during starvation in suspension culture.
  
  
  METHODS
  Here, we have assessed the hypothesis that htt may be a genetic interactor of csaA, a major regulator of EDTA-resistant homotypic cell adhesion in D. discoideum. Immunoblot analysis demonstrated that csaA protein expression is dysregulated in htt- cells.
  
  
  RESULTS
  Unexpectedly, csaA overexpression, previously shown to rescue csaA- cell adhesion, failed to rescue the htt- adhesion defect. Thus, while htt was required for proper expression of the csaA protein, csaA overexpression was not sufficient to confer EDTA-resistant adhesion in the context of the htt- genetic background in contrast to parental cells. This implies a novel role for htt in conferring csaA-dependent, EDTA-resistant cell adhesion that warrants further investigation. Calcium supplementation restored both endogenous csaA protein levels and EDTA-resistant adhesion in htt- cells.
  
  
  CONCLUSIONS
  Our data suggests the existence of an additional mechanism that overcomes the EDTA-resistant adhesion defect of htt- cells in the early development of D. discoideum.
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Morgan N
authors.initials: MN
authors.lastname: Thompson
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Marcy E
authors.initials: ME
authors.lastname: MacDonald
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Myre
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology / Q000502:physiology*; D004492:Edetic Acid / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D015800:Protozoan Proteins; D004492:Edetic Acid
keywords: Cell adhesion; Dictyostelium discoideum; calcium; contact site A; csA; csaA; development; gp80; hd; htt; huntingtin