A Novel Gelsolin Isoform Expressed by Oligodendrocytes in the Central Nervous System

Abstract

Two isoforms of the Ca2+‐sensitive, actin‐binding protein gelsolin have been identified thus far; one is an intracellular protein, cytoplasmic gelsolin, and the other is a secretory protein called plasma gelsolin. Gelsolin expression in the mammalian CNS appears to be localized mainly to oligodendrocytes where it is presumed that the cytoplasmic isoform predominates. Here, we show that oligodendrocytes not only contain cytoplasmic gelsolin, but they also express a novel gelsolin isoform that we have named gelsolin‐3. Cytoplasmic gelsolin, plasma gelsolin, and gelsolin‐3 arise by alternative splicing from the same gene. The N‐terminal amino acid sequence unique to gelsolin‐3 is shown to be encoded by a single exon in a region previously thought to be an intron in the human gelsolin gene. In situ hybridization analysis confirmed that gelsolin‐3 mRNA is localized primarily to oligodendrocytes in rat brain. In other tissues, gelsolin‐3 shows a more restricted pattern of expression than cytoplasmic gelsolin. These data support the view that the gelsolin isoforms have differential roles in the regulation of the actin cytoskeleton.

Inhibition of Alzheimer's amyloid-β peptide-induced reduction of mitochondrial membrane potential and neurotoxicity by gelsolin

“…A set of 19-mer oligonucleotides (CGGTGACTGCTTCATTCTG) corresponding to nucleotides 640 downstream of the transcription start site was selected from the rat gelsolin open reading frame (ORF) sequence [33]. We confirmed that the selected oligonucleotide set did not have homology to any other genes by a BLAST search, so that they would not interfere with other genes.…”

Gelsolin superfamily proteins: key regulators of cellular functions

“…Recently, a third isoform (gelsolin-3) has been described [9]. Gelsolin-3 is cytoplasmic and is characterized by 11 additional residues at the N-terminus.…”

“…Gelsolin-3 is cytoplasmic and is characterized by 11 additional residues at the N-terminus. Gelsolin-3 is expressed in oligodendrocytes and mainly in the brain, lungs and testis [9], but its specific function is still unknown. Absence of an indication means absence of studies addressing the specific role of a protein in the cellular process concerned.…”

Gelsolin is required for macrophage recruitment during remyelination of the peripheral nervous system

“…There are three isoforms of gelsolin encoded by the same gene (Kwiatkowski et al, 1986): two are intracellular proteins, cytoplasmic gelsolin and gelsolin-3, which appear to be restricted mainly to cells of oligodendroglial lineage (Vouyiouklis and Brophy, 1997), and a third form that is secreted and present in the plasma of vertebrates. Although Gelsolin mutant mice are viable and fertile, they display defects in postnatal mammary gland development, in the organization of actin-based domains in osteoclasts, in the formation of the growth cone of neuritis, and in the migratory capacity of neutrophils during inflammation, among others (Witke et al, 1995).…”