title: Role of glycosaminoglycans in determining the helicity of paired helical filaments.
abstract: It is known from previous work that tau is the main component of paired helical filaments (PHFs) and that it can assemble in vitro into polymers resembling PHFs when high concentrations of protein are used. In the search for molecules that can facilitate tau polymerization, a component of neurofibrillary tangles, heparan sulfate (or its more sulfated form, heparin), and other glycosaminoglycans have been tested. Glycosaminoglycans, in the sulfated but not in the unsulfated form, facilitate not only tau assembly but also the formation of polymers resembling PHFs. Conversely, PHFs were found to contain heparan sulfate and chondroitin sulfate. Heparinase or chondroitinase treatment of PHFs results in the formation of straight structures. All of these results suggest a role for sulfated glycosaminoglycans in determining the helicity of PHFs.
authors.affiliation: Centro de Biología Molecular (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Arrasate
authors.forename: M
authors.initials: M
authors.lastname: Pérez
authors.forename: J M
authors.initials: JM
authors.lastname: Valpuesta
authors.forename: J
authors.initials: J
authors.lastname: Avila
mesh_terms: D001665:Binding Sites; D002808:Chondroitin Lyases / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000032:analysis / Q000737:chemistry* / Q000276:immunology; D019763:Heparin Lyase / Q000378:metabolism; D006497:Heparan Sulfate / Q000032:analysis / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D016253:Microscopy, Immunoelectron; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000276:immunology / Q000648:ultrastructure; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D002808:Chondroitin Lyases; D002809:Chondroitin Sulfates; D019763:Heparin Lyase; D006497:Heparan Sulfate; D011994:Recombinant Proteins; D016875:tau Proteins