PTL-1, A CAENORHABDITIS-ELEGANS GENE WHOSE PRODUCTS ARE HOMOLOGOUS TOTHE TAU-MICROTUBULE-ASSOCIATED PROTEINS

The tau microtubule-associated proteins are axonal proteins that have been implicated in axonal outgrowth, microtubule spacing, and microtub ule bundling. Moreover, tau is the major structural component of the p aired helical filaments present in the brains of Alzheimer's disease p atients. The Caenorhabditis elegans Genome Sequencing Consortium ident ified a genomic sequence with homology to the repeat region of tau. PC R, Northern analyses, and cDNA sequencing were used here to identify t ranscripts containing the tau homology region. The gene that encodes t hese transcripts was named ptl-1 for protein with E-like repeats. The ptl-1 transcript, like mammalian tau transcripts, is alternatively spl iced to produce messages that encode proteins with variable numbers of repeats. The predicted ptl-1 products have strong sequence homology t o tau over the repeat region and are similar to tau in several other i mportant respects including size, amino acid content, charge distribut ion, predicted secondary structure, hydrophobicity, and flexibility. B oth proteins contain several potential glycosylation sites and numerou s phosphorylation sites. Bacterially expressed PTL-1 bound to microtub ules in vitro. These results show that tau-like proteins evolved early and suggests that they may be present in many different phyla. C. ele gans is a powerful system amenable to genetic, molecular, and cellular analysis in which to study the functions of this important class of p roteins.