A two-hybrid screening of human Tau protein: interactions with Alu-derived domain.
The microtubule associated protein tau has been implicated in several neurodegenerative diseases, grouped as tauopathies. To search for tau-associated proteins, the two-hybrid system was used with tau as a bait and an adult human brain cDNA library as a source of putative interacting proteins. We have identified two positive clones consisting of an Alu-derived amino acid sequence that binds to tau and show moderate homology with a motif found in several neuronal proteins related to neurodegenerative disorders. We have also demonstrated that the Alu-derived motif interacts in vitro with tau and may be involved in modulation of its phosphorylation. These findings suggest the existence of tau-binding proteins that are able to bind to tau through their Alu-derived sequence in a direct way. The possible interaction of these proteins with tau could play a role in its cellular localization, regulate the amount of phosphorylated tau and also be involved in the pathological processes of tauopathies.
Hoenicka
Janet
J
Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid 28049, Spain.
Arrasate
Montserrat
M
de Yebenes
Justo Garcia
JG
Avila
Jesús
J
D020087:Alu Elements / Q000235:genetics*; D000595:Amino Acid Sequence; D002846:Chromatography, Affinity; D018076:DNA, Complementary / Q000235:genetics; D005696:Galactosidases / Q000737:chemistry; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
C109804:AD7c-NTP; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D010455:Peptides; D016875:tau Proteins; D005696:Galactosidases