The Caenorhabditis elegans Ldb/NLI/Clim Orthologue ldb-1 Is Required for Neuronal Function

Abstract

LIM homeodomain (LIM-HD) and nuclear LIM-only proteins play important roles in a variety of developmental processes in animals. In some cases their activities are modulated by a nuclear LIM binding protein family called Ldb/NLI/Clim. Here we characterize the Ldb/NLI/Clim orthologue ldb-1 of the nematode Caenorhabditis elegans. Two alternatively spliced variants exist, which differ in their amino-termini. The ldb-1 orthologue of Caenorhabditis briggsae has the same structure as that of C. elegans and is highly conserved throughout the open reading frame, while conservation to fly and vertebrate proteins is restricted to specific domains: the dimerization domain, the nuclear localization sequence, and the LIM interaction domain. C. elegans ldb-1 is expressed in neurogenic tissues in embryos, in all neurons in larval and adult stages, and in vulval cells, gonadal sheath cells, and some body muscle cells. C. elegans LDB-1 is able to specifically bind LIM domains in yeast two-hybrid assays. RNA inactivation studies suggest that C. elegans ldb-1 is not required for the differentiation of neurons that express the respective LIM-HD genes or for LIM-HD gene autoregulation. In contrast, ldb-1 is necessary for several neuronal functions mediated by LIM-HD proteins, including the transcriptional activation of mec-2, the mechanosensory neuron-specific stomatin.

The C. elegans LIM homeobox gene lin-11 specifies multiple cell fates during vulval development

“…Using a conditional RNAi approach, we have examined lin-11 function during vulval morphogenesis and demonstrate that lin-11 is required in vulval progeny for wild-type patterning. Finally, we show that the LIM-binding protein LDB-1 (Cassata et al, 2000) plays a role in vulval differentiation by directly interacting with LIN-11.…”

“…ldb-1::GFP expression is first detected in embryos towards the end of gastrulation (prior to the comma stage) and is seen in the vulval cells among other expression (Cassata et al, 2000) (not shown). In vulval cells ldb-1::GFP expression is observed in both the 1°as well as 2°lineage cells (Fig.…”

“…Among the co-factors are the LIM-binding proteins represented by NLI/Ldb1/CLIM2, which display highly specific interactions with the LIM domains. The C. elegans LIM-binding protein LDB-1 has been shown to interact with two LIM homeodomain proteins CEH-14 and MEC-3 (Cassata et al, 2000). As it is the only known LIM-binding protein in C. elegans, it is likely that LDB-1 regulates the activities of other LIM homeodomain proteins, including LIN-11.…”

The role of the proline-rich domain of Ssdp1 in the modular architecture of the vertebrate head organizer

“…Although we cannot categorically rule out the alternative scenario that an ancient Ssdp protein gained a new functional proline-rich domain before invertebrate and vertebrate separation and that Ldb1 lost the consequently redundant element, the functional data confirm our model of the evolutionary change in the nematode lineage. It has been shown that Ldb1 is actively expressed during C. elegans development, that it is required for some neuronal function, and that knockdown of its expression by RNA interference leads to uncoordinated locomotion (8). However, Ssdp is expressed at a low level, and its RNA interference shows no obvious phenotype (29).…”

“…The fundamental and universal nature of this interaction is clear from evolutionary comparisons. The Ldb1 ortholog in Caenorhabditis elegans is also able to bind LIM domains (8), and Chip, the Drosophila homolog of Ldb1, can interact with fly and mammalian LIM proteins (9).…”