SUT-1 enables tau-induced neurotoxicity in C. elegans.
We previously reported a transgenic Caenorhabditis elegans model for tauopathies in which expression of human tau in neurons caused insoluble phosphorylated tau accumulation, neurodegeneration and uncoordinated movement (Unc). To identify genes participating in tau neurotoxicity, we conducted a forward genetic screen for mutations that ameliorate tau-induced uncoordination. The recessive mutation sut-1(bk79) partially suppresses the Unc phenotype, tau aggregation and neurodegenerative changes caused by tau. We identified the sut-1 gene and found it encodes a novel protein. We conducted a yeast two hybrid screen to identify SUT-1 binding partners and found UNC-34, the C. elegans homolog of the cytoskeletal regulatory protein Enabled (ENA). In vitro protein binding assays and genetic studies validated the interaction between SUT-1 and UNC-34. The SUT-1/UNC-34 protein-protein interaction plays a role in both the normal function of UNC-34 and in the tau-induced phenotype. Thus, we have found a conserved molecular pathway participating in tau neurotoxicity in C. elegans.
Kraemer
Brian C
BC
Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA. kraemerb@u.washington.edu
Schellenberg
Gerard D
GD
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D053263:Gene Regulatory Networks; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D024801:Tauopathies / Q000235:genetics* / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; C524780:SUT-1 protein, C elegans; D016875:tau Proteins; C511070:unc-34 protein, C elegans