<i>ptl-1</i>, a<i>Caenorhabditis elegans</i>Gene Whose Products Are Homologous to the τ Microtubule-Associated Proteins^,

Abstract

The tau microtubule-associated proteins are axonal proteins that have been implicated in axonal outgrowth, microtubule spacing, and microtubule bundling. Moreover, tau is the major structural component of the paired helical filaments present in the brains of Alzheimer's disease patients. The Caenorhabditis elegans Genome Sequencing Consortium identified a genomic sequence with homology to the repeat region of tau. PCR, Northern analyses, and cDNA sequencing were used here to identify transcripts containing the tau homology region. The gene that encodes these transcripts was named ptl-1 for protein with tau-like repeats. The ptl-1 transcript, like mammalian tau transcripts, is alternatively spliced to produce messages that encode proteins with variable numbers of repeats. The predicted ptl-1 products have strong sequence homology to tau over the repeat region and are similar to tau in several other important respects including size, amino acid content, charge distribution, predicted secondary structure, hydrophobicity, and flexibility. Both proteins contain several potential glycosylation sites and numerous phosphorylation sites. Bacterially expressed PTL-1 bound to microtubules in vitro. These results show that tau-like proteins evolved early and suggests that they may be present in many different phyla. C. elegans is a powerful system amenable to genetic, molecular, and cellular analysis in which to study the functions of this important class of proteins.