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Matrix Biol,
2000]
Integrins are essential for the development of the two genetically tractable invertebrate model organisms, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Just two integrins are present in C. elegans: one putative RGD binding integrin alphapat-2betapat-3, corresponding to Drosophila alphaPS2betaPS and vertebrate alpha5beta1, alphaVbeta1 and alpha8beta1, and one putative laminin binding integrin alphaina-1betapat-3, corresponding to Drosophila alphaPS1betaPS and vertebrate alpha3beta1, alpha6beta1 and alpha7beta1. In this review, the function of this minimal set of integrins during the development of these two invertebrates is compared. Despite the differences in bodyplan and developmental strategy, integrin adhesion to the extracellular matrix is required for similar processes: the formation of the link that translates muscle contraction into movement of the exoskeleton, cell migration, and morphogenetic interactions between epithelia. Other integrin functions, such as regulation of gene expression, have not yet been experimentally demonstrated in both organisms. Additional proteins have been characterised in each organism that are essential for integrin function, including extracellular matrix ligands and intracellular interacting proteins, but so far different proteins have been found in the two organisms. This in part represents the fact that the characterisation of the full set of interacting proteins is not complete in either system. However, in other cases different proteins appear to be used for similar functions in the two animals. The continued use of genetic approaches to identify proteins required for integrin function in these two model organisms should lead to the identification of the minimal set of conserved components that form integrin adhesive structures.
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Curr Opin Cell Biol,
2000]
Integrins have the ability to organise macromolecular structures both inside and outside the cell. Analysis of integrin function in the developing embryos of worms and flies suggests that, although the extracellular matrix directs integrins to organise intracellular proteins, the cytoskeleton may have the first word.
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Dev Cell,
2002]
Integrins are cell surface receptors of the extracellular matrix present in all animals. Genetic analysis in worms, flies, and vertebrates has revealed integrin involvement in key developmental processes, and we focus here on examples of integrin functions that are comparable across these model organisms. Integrins contribute to cell movement by providing traction to migrating cells, through assembly of extracellular matrices that can serve as tracks for migration, and by transmitting guidance signals that direct cells or cell processes to their targets. Integrins also participate in signaling events that govern tissue differentiation and organogenesis. Finally, adhesion by integrin-mediated junctions allows tissues to withstand mechanical load and is essential for tissue integrity.
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J Cell Sci,
2002]
Recent studies have characterised a family of giant cytoskeletal crosslinkers encoded by the short stop gene in Drosophila and the dystonin/BPAG1 and MACF1 genes in mammals. We refer to the products of these genes as spectraplakins to highlight the fact that they share features with both the spectrin and plakin superfamilies. These genes produce a variety of large proteins, up to almost 9000 residues long, which can potentially extend 0.4 micro m across a cell. Spectraplakins can interact with all three elements of the cytoskeleton: actin, microtubules and intermediate filaments. The analysis of mutant phenotypes in BPAG1 in mouse and short stop in Drosophila demonstrates that spectraplakins have diverse roles. These include linking the plasma membrane and the cytoskeleton, linking together different elements of the cytoskeleton and organising membrane domains.
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J Bioenerg Biomembr,
1993]
The ADP/ATP, phosphate, and oxoglutarate/malate carrier proteins found in the inner membranes of mitochondria, and the uncoupling protein from mitochondria in mammalian brown adipose tissue, belong to the same protein superfamily. Established members of this superfamily have polypeptide chains approximately 300 amino acids long that consist of three tandem related sequences of about 100 amino acids. The tandem repeats from the different proteins are interrelated, and probably have similar secondary structures. The common features of this superfamily are also present in nine proteins of unknown functions characterized by DNA sequencing in various species, most notably in Caenorhabditis elegans and Saccharomyces cerevisiae. The high level expression in Escherichia coli of the bovine oxoglutarate/malate carrier, and the reconstitution of active carrier from the expressed protein, offers encouragement that the identity of superfamily members of known sequence but unknown function may be uncovered by a similar route.
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Traffic,
2003]
Proteins must be correctly folded and assembled to fulfill their functions as assigned by genetic code. All living cells have developed systems to counteract protein unfolding or misfolding. A typical example of such a homeostatic response is triggered when unfolded proteins are accumulated in the endoplasmic reticulum. Eukaryotic cells cope with endoplasmic reticulum stress by attenuating translation, generally to decrease the burden on the folding machinery, as well as by inducing transcription of endoplasmic reticulum-localized molecular chaperones and folding enzymes to augment folding capacity. These translational and transcriptional controls are collectively termed the unfolded protein response. The unfolded protein response is unique in that the molecular mechanisms it uses to transmit signals from the endoplasmic reticulum lumen to the nucleus are completely different from those used for signaling from the plasma membrane. Frame switch splicing (a term newly proposed here) and regulated intramembrane proteolysis (proposed by Brown et al., Cell 2000; 100: 391-398) employed by the unfolded protein response represent novel ways to activate a signaling molecule post-transcriptionally and post-translationally, respectively. They are critically involved in various cellular regulation pathways ranging from bacterial extracytoplasmic stress response to differentiation of mature B cells into antibody-secreting plasma cells. Further, mammalian cells take advantage of differential properties between the two mechanisms to determine the fate of proteins unfolded or misfolded in the endoplasmic reticulum. This review focuses on the transcriptional control that occurs during the unfolded protein response in various species.