Structure of an invertebrate gene encoding cytoplasmic intermediate filament (IF) proteins: implications for the origin and the diversification of IF proteins.

Abstract

The structure of the single gene encoding the cytoplasmic intermediate filament (IF) proteins in non‐neuronal cells of the gastropod Helix aspersa is described. Genomic and cDNA sequences show that the gene is composed of 10 introns and 11 exons, spanning greater than 60 kb of DNA. Alternative RNA processing accounts for two mRNA families which encode two IF proteins differing only in their C‐terminal sequence. The intron/exon organization of the Helix rod domain is identical to that of the vertebrate type III IF genes in spite of low overall protein sequence homology and the presence of an additional 42 residues in coil 1b of the invertebrate sequence. Intron position homology extends to the entire coding sequence comprising both the rod and tail domains when the invertebrate IF gene is compared with the nuclear lamin LIII gene of Xenopus laevis presented in the accompanying report of Döring and Stick. In contrast the intron patterns of the tail domains of the invertebrate IF and the lamin genes differ from those of the vertebrate type III genes. The combined data are in line with an evolutionary descent of cytoplasmic IF proteins from a nuclear lamin‐like progenitor and suggest a mechanism for this derivation. The unique position of intron 7 in the Helix IF gene indicates that the archetype IF gene arose by the elimination of the nuclear localization sequence due to the recruitment of a novel splice site. The presumptive structural organization of the archetype IF gene allows predictions with respect to the later diversification of metazoan IF genes. Whereas models proposing a direct derivation of neurofilament genes seem unlikely, the earlier speculation of an mRNA transposition mechanism is compatible with current results.

O-Sulfonation of Serine and Threonine

“…Peptide sequences were deduced by de novo interpretation of their CID mass spectra and used to query genomic databases to assign tentative homologies in sequenced genomes where possible. This effort revealed a number of protein spots with extensive homology to intermediate filament proteins from other mollusks, including Helix (20) and Aplysia (21). During the course of carrying out de novo sequencing of these particular proteins, a number of digest components were discovered from analysis of an LC-ESI-CID-MS experiment that displayed identical mass values for their entire CID sequence ion series (viz.…”

Introducing intermediate filaments: from discovery to disease

“…genes encoding cytoplasmic IFs suggests that all IF proteins are derived from a lamin-like progenitor (47,48). Early cross-linking experiments showed that the nuclear lamins can form oligomeric structures (42,49).…”

Intermediate filaments in Caenorhabditis elegans

“…The rod domain is further divided into subdomains 1a, 1b, 2a, and 2b, which are separated by short linker regions referred to as L1, L12, and L2. The cytoplasmic C. elegans IF polypeptides are distinguished by an elongated coil 1b with 42 extra residues which is typical for protostomia and is also a feature shared by all lamins [Weber et al, 1989;Dodemont et al, 1990Dodemont et al, , 1994. Furthermore, the A-and B-type IFs also contain an additional, 110 amino acid-long globular Ig-like fold lamin-homology segment in the tail domain [Weber et al, 1989;Karabinos et al, 2001].…”