QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Summary Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Palmgren, S. Articles by Lappalainen, P. Search for Related Content PubMed PubMed Citation Articles by Palmgren, S. Articles by Lappalainen, P.

Twinfilin, a molecular mailman for actin monomers

Program in Cellular Biotechnology, Institute of Biotechnology, PO Box 56, 00014 University of Helsinki, Finland

View larger version (44K): [in a new window]   Fig. 1. The domain structure of twinfilin. (A) Twinfilin is composed of two domains homologous to the ADF/cofilin proteins (ADF-H domain), separated by a short, 30 amino acid, linker and followed by a C-terminal tail region. The ADF-H domains are approximately 20% identical to each other, and they both appear to be involved in interactions with actin monomers. (B) A phylogenetic tree of twinfilin ADF-H domains from different species as produced by Clustal-X software. The N-terminal and C-terminal ADF-H domains of twinfilins from different species form two independent branches in the tree, demonstrating that each one of the ADF-H domains between different species are more homologous than the N- and C-terminal ADF-H domains within any particular twinfilin. This suggests that the two ADF-H domains of twinfilin were already present before the divergence of fungal and animal lineages. Databases and accession numbers for twinfilin sequences are: S. pombe twinfilin (EMBL, AL034490); S. cerevisiae twinfilin (EMBL, Z72865); C. elegans twinfilin (EMBL, U46668); D. melanogaster twinfilin (EMBL, AE003703); H. sapiens twinfilin-1 (PIR, A55922); H. sapiens twinfilin-2 (EMBL, Y17169); M. musculus twinfilin-1 (GenBank, U82324); and M. musculus twinfilin-2 (EMBL, Y17808).

View larger version (92K): [in a new window]   Fig. 2. Effects of mutations in yeast and Drosophila twinfilin. The most obvious phenotype of twinfilin deletion (twf) yeast strains is the random bipolar budding pattern. Wild-type diploid yeast cells (A) show a bipolar budding pattern, whereas the bud-scars, as visualized by calcofluor staining, show random distribution in twf/twf yeast cells (B). A strong hypomorphic mutation in the Drosphila twinfilin gene results in multiple morphological defects, including aberrant bristle morphology. In wild-type flies (C) the macrochaetae (arrows) are straight and show regular longitudinal groove and ridge structures. In twinfilin mutant flies (D) the macrochaetae (arrows) are often bent and show irregular surface morphology. Bars, 5 µm (A,B); 25 µm (C,D).

View larger version (60K): [in a new window]   Fig. 3. A model for the role of twinfilin in actin filament turnover. ADF/cofilin feeds new monomers to the cytoplasmic pool by depolymerizing actin filaments at their minus-ends. Because twinfilin binds ADP-actin-monomers with a high affinity and through an overlapping interface with ADF/cofilin, it may sequester actin monomers from ADF/cofilin. Twinfilin inhibits the spontaneous nucleotide exchange on actin monomers and may localize actin monomers, in their inactive ADP-form, to the sites of rapid actin filament assembly. The localization of twinfilin to the sites of rapid actin filament assembly is mediated through interactions with capping protein. After localization, the ADP-actin-monomer is released from twinfilin and subsequent nucleotide exchange and assembly into the plus-end of the filament may be catalyzed by profilin. The activities of cofilin, profilin and twinfilin are downregulated by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2).