Ohta, Akane et al. (2021) International Worm Meeting "Solute Carrier family 46 and aquarius intron-binding spliceosomal factor mediates temperature tolerance"

Ohta, Akane, Kuhara, Atsushi, Mizuno, Satomi, Isono, Kazuho, Mima, Sunao, Taji, Teruaki, Sato, Yuki, Yamashiro, Serina

[International Worm Meeting, 2021]

Liu Z et al. (2010) Biochemistry "Distinct roles of four gelsolin-like domains of Caenorhabditis elegans gelsolin-like protein-1 in actin filament severing, barbed end capping, and phosphoinositide binding."

Klaavuniemi T, Ono S, Liu Z

[Biochemistry, 2010]

Caenorhabditis elegans gelsolin-like protein-1 (GSNL-1) is a new member of the gelsolin family of actin regulatory proteins [Klaavuniemi, T., Yamashiro, S., and Ono, S. (2008) J. Biol. Chem. 283, 26071-26080]. It is an unconventional gelsolin-related protein with four gelsolin-like (G) domains (G1-G4), unlike typical gelsolin-related proteins with three or six G domains. GSNL-1 severs actin filaments and caps the barbed end in a calcium-dependent manner similar to that of gelsolin. In contrast, GSNL-1 has properties different from those of gelsolin in that it remains bound to F-actin and does not nucleate actin polymerization. To understand the mechanism by which GSNL-1 regulates actin dynamics, we investigated the domain-function relationship of GSNL-1 by analyzing activities of truncated forms of GSNL-1. G1 and the linker between G1 and G2 were sufficient for actin filament severing, whereas G1 and G2 were required for barbed end capping. The actin severing activity of GSNL-1 was inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2), and a PIP2-sensitive domain was mapped to G1 and G2. At least two actin-binding sites were detected: a calcium-dependent G-actin-binding site in G1 and a calcium-independent G- and F-actin-binding site in G3 and G4. These results reveal both conserved and different utilization of G domains between C. elegans GSNL-1 and mammalian gelsolin for actin regulatory functions.

Hoffman, Corey et al. (2011) International Worm Meeting "The minus-end actin capping protein, TMD-1/tropomodulin, regulates the morphology of the intestine and excretory cell."

Ling, Clarence, Mantione, Gary, Hoffman, Corey, Gallagher, Thomas, Cannataro, Vincent, Cox, Elisabeth (Abbi), Vissichelli, Nicole

[International Worm Meeting, 2011]

Tropomodulins are actin regulatory proteins that interact with the slow-growing end of actin filaments and also have actin nucleating activity. C. elegans has a tropomodulin homolog, TMD-1/UNC-94 that encodes two isoforms with sequence similarity to vertebrate tropomodulins. TMD-1 is involved in body wall muscle development1,2; and we have found that it is also needed for proper morphology of the intestine and excretory cell. In the intestine, TMD-1 localizes to the terminal web, which is an actin and intermediate filament rich structure that underlies the apical membrane facing the lumen. In the intestine, loss of tmd-1 function results in flattened morphology of the lumen and a reduction in intestinal lumen volume. Interestingly, the intestinal defects can be rescued by performing weak RNAi for the myosin phosphatase, mel-11, suggesting a potential role for TMD-1 in promoting proper actomyosin contractility levels in the terminal web. More globally, this points to an important and previously undocumented role for actomyosin contractility in regulating lumen shape of simple endothelial tubes. tmd-1(tm724) mutants, which carry a large deletion in the tmd-1 gene, also have excretory cell defects; specifically the canals fail to extend properly. Improper structure of the intestine and excretory cell may account for the larval lethality, patchy appearance, and slow growth exhibited by tmd-1(tm724) mutants. This work indicates an important role for TMD-1/tropomodulin in morphogenesis of tubular epithelial tissues. 1 Yamashiro et al. (2008) J. Cell Sci. 121: 3867-77. 2 Stevensen et al. (2007) J. Mol. Bio. 374: 936-50.

Cannataro, Vincent et al. (2009) International Worm Meeting "TMD-1 / Tropomodulin Regulates Intestinal Lumen Diameter in C. elegans."

Silva, Malan, Cannataro, Vincent, Gallagher, Thomas, Cox, Elisabeth

[International Worm Meeting, 2009]

Tubes are a central architectural feature of many human tissues including glands, the urogenital and gastrointestinal tracts, the respiratory tract and the vascular system. Despite their importance, much remains unknown about the molecular mechanisms involved in tube development. This work explores a new role for tropomodulins in regulation of endothelial tube formation. Tropomodulins are one of the few proteins known to regulate the slow growing ends of actin filaments. The C. elegans tmd-1 gene encodes two transcripts (tmd-1a and tmd-1b) that have similar domain structure to mammalian tropomodulins. We have been examining the role of TMD-1 in development of the C. elegans intestine, which is a relatively simple, transparent tube that forms by a cord-hollowing mechanism similar to that used by some capillaries and renal tubules. Antibody staining using a rabbit anti-TMD-1 antibody demonstrates that TMD-1 localizes to the luminal surface of the C. elegans intestine as it undergoes morphogenesis. Interestingly, embryos homozygous for the tmd-1(tm724) allele, which contains a large deletion that affects both transcripts1, exhibit areas of intestinal lumen diameter that are 65% larger than wild-type. tmd-1(sf20) homozygous mutants, which have a premature stop codon affecting both transcripts2, also exhibit luminal expansions (50% larger than wild-type). Currently, investigations are underway to determine the molecular mechanisms by which TMD-1 regulates intestinal lumen diameter. Possibilities include modulation of actomyosin contractility, cooperation with the actin-spectrin cytoskeleton to provide mechanical strength to the luminal surface, and/or regulation of vesicle trafficking. This work is supported by National Institutes of Health grant R15HD059952. 1 Yamashiro et al. (2008) J. Cell Sci. 121: 3867-77. 2 Stevensen et al. (2007) J. Mol. Bio. 374: 936-50.