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Trends Genet,
2000]
An ADAM is a transmembrane protein that contains a disintegrin and metalloprotease domain and, therefore, it potentially has both cell adhesion and protease activities. Currently, the ADAM gene family has 29 members, although the function of most ADAM gene products is unknown. We discuss the ADAM gene products with known functions that act in a highly diverse set of biological processes, including fertilization, neurogenesis, myogenesis, embryonic TGF-alpha release and the inflammatory response.
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Biol Chem,
2006]
The conserved oligomeric Golgi (COG) complex is an octameric protein complex associated with the Golgi apparatus and is required for proper sorting and glycosylation of Golgi resident enzymes and secreted proteins. Although COG complex function has been extensively studied at the cellular and subcellular levels, its role in animal development mostly remains unknown. Recently, mutations in the components of the COG complex were found to cause abnormal gonad morphogenesis in Caenorhabditis elegans. In C. elegans, the COG complex acts in the glycosylation of an ADAM (a disintegrin and metalloprotease) family protein, MIG-17, which directs migration of gonadal distal tip cells to lead gonad morphogenesis. This is the first link between the COG complex and the function of an ADAM protease that is directly involved in organ morphogenesis, demonstrating the potential of C. elegans as a model system to study COG function in animal development.
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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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Arch Med Res,
2001]
Fusion between gametes is a key event in the fertilization process involving the interaction of specific domains of the sperm and egg plasma membranes. During recent years, efforts have been made toward the identification of the specific molecular components involved in this event. The present work will focus on the best characterized candidates for mediating gamete membrane fusion in mammals. These molecules include members of the ADAM (a disintegrin and a metalloprotease domain) family, i.e., testicular proteins fertilin alpha, fertilin beta, and cyritestin, which are thought to interact with integrins in the egg plasma membrane through their disintegrin domains, and a member of the cysteine-rich secretory proteins (CRISP) family, i.e., epididymal protein DE, which participates in an event subsequent to sperm-egg binding and leading to fusion through specific complementary sites localized on the fusogenic area of the egg surface. The identification and characterization of these molecules will contribute not only to a better understanding of the molecular mechanisms underlying mammalian sperm-egg fusion but also to the development of new methods for both fertility regulation and diagnosis and treatment of human infertility.
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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.