BioEssays

doi: 10.1002/bies.950141101pmid: N/A

doi: 10.1002/bies.950141118pmid: N/A

Crawford, Fiona; Goate, Alison

doi: 10.1002/bies.950141102pmid: 1365885

The last year has seen major advances in the study of Alzheimer's disease (AD).† Four mutations involving amino acid substitutions in axons 16 and 17 of the amyloid precursor protein (APP) gene, have been identified which co‐segregate with the disease in some families multiply affected by early onset Alzheimer's disease. These mutations are strongly suggestive of a causative role for the amyloid preursor protein in Alzheimer's disease. Despite their rarity, these mutations are important because they represent the first known cause of Alzheimer's disease. Processing of APP must be central to the pathogenesis of the disease although the precise effects of these amino acid substitutions are not understood. Work is now being undertaken to characterise the processing pathways of APP and to identify other causes of AD. The development of models of AD using the APP mutations offers the possibility of identifying drug targets and developing more effective treatments than are presently available.

Adler, Paul N.

doi: 10.1002/bies.950141103pmid: 1365886

The cuticular surface of Drosophila is decorated by parallel arrays of polarized structures such as hairs and sensory bristles; for example, on the wing each cell produces a distally pointing hair. These patterns are termed (tissue polarity). Several genes are known whose activity is essential for the development of normal tissue polarity. Mutations in these genes alter the orientation of the hair or bristle with respect to neighboring cells and the body as a whole. The phenotypes of mutations in these genes allows them to be placed in three phenotypic groups. Based on their behavior in genetic mosaics, it has proved possible to determine that individual genes are required either for the generation of an intercellular polarity signal and/or the transduction of that signal to the cytoskeleton.

Pouliot, Yannick

doi: 10.1002/bies.950141104pmid: 1365887

Cadherins are a multigene family of proteins which mediate homophilic calcium‐dependent cell adhesion and are thought to play an important role in morphogenesis by mediating specific intercellular adhesion. Different lines of experimental evidence have recently indicated that the site responsible for mediating adhesive interactions is localized to the first extracellular domain of cadherin. Based upon an analysis of the sequence of this domain, I show that cadherins can be classified into three groups with distinct structural features. Furthermore, using this sequence information a phylogenetic tree relating the known cadherins was assembled. This is the first such tree to be published for the cadherins. One cadherin subtype, neural cadherin (N‐cadherin), shows very little sequence divergence between species, whereas all other cadherin subtypes show more substantial divergence, suggesting that selective pressure upon this domain may be greater for N‐cadherin than for other cadherins. Phylogenetic analysis also suggests that the gene duplications which established the main branches leading to the different cadherin subtypes occurred very early in their history. These duplications set the stage for the diversified superfamily we now observe.

Brown, W. M.; Dziegielewska, K. M.; Saunders, N. R.; Møsllgård, K.

doi: 10.1002/bies.950141105pmid: 1285422

Bovine fetuin, the first fetal protein to be described, has recently been shown to be a species homologue of a well known human plasma protein ‐ α2HS glycoprotein (α2HS). The fetuins are now known to be members of the cystatin superfamily. The structural properties of the six fetuins that have been fully sequenced are compared. Despite the structural homology of these proteins, their described properties in the literature make them appear to be quite different. The diverse in vitro properties claimed for fetuin/α2HS are reviewed. In vivo, fetuins are involved in the acute phase response. In development, in all species studied so far, fetuins are present in a specific cell population that forms the developing neocortex. The possible functional significance of this distribution is discussed.

Maloney, Peter C.

doi: 10.1002/bies.950141106pmid: 1365888

This article summarizes the study of anion exchange mechanisms in bacteria. Along with defining at least two different families of anion exchange, an examination of such carrier‐mediated antiport reactions has led to techniques that considerably broaden the scope of biochemical methods for examining membrane proteins. Such advances have been exploited to show that anion exchange itself forms the mechanistic base of an entirely new kind of proton pump, one which may shed light on a variety of bacterial events, including methanogenesis. Perhaps most important, the study of exchange provided the final link in a chain of evidence pointing to a structural (rhythm) that seems to characterize membrane carriers. These three issues ‐ a biochemical tool, a new proton pump, and a common structural rhythm ‐ are briefly examined in the context of their origins in the analysis of bacterial anion exchange.

doi: 10.1002/bies.950141107pmid: N/A

Poulton, Jo

doi: 10.1002/bies.950141108pmid: 1365889

Since the human mitochondrial genome was characterised and sequenced in 1981(1), it has been viewed as the likely site of genetic diseases showing a maternal inheritance pattern and associated with defects of the respiratory chain, such as the mitochondrial myopathies (MMs)†(2). The properties that make it a candidate for the source of such conditions are that it encodes polypeptides involved in electron transport(3,4) and that it is maternally inherited(5). However, several of the mtDNA diseases only fulfill one or other of these criteria: the first group of mtDNA diseases showed Only sporadic deletions(6,7), and the first point mutation in Leber's Hereditary Optic Neuropathy(8) (LHON) is not associated with a clear biochemical defect. Furthermore, it is now clear that both autosomal dominant(9) and probably recessive(10) nuclear genes can cause abnormalities of mtDNA. Each of these major groups will be considered in turn.

Sleigh, Merilyn J.

doi: 10.1002/bies.950141109pmid: 1365890

How cell commitment and differentiation are controlled in the early stages of embryogenesis is a problem that has long fascinated developmental biologists. Retinoic acidinduced differentiation of embryonal carcinoma cells in culture provides a model in which these questions can be explored. Recent work has yielded exciting insights into the central series of molecular changes which drives the commitment of these cells to formation of a new phenotype. Interacting with the key molecules in this central pathway is a variety of transcription factors, many of which show changes in availability and/or activity during differentiation. In various combinations, these modulate the activities of genes involved in both cell proliferation and in the production of extracellular matrix and other proteins characteristic of differentiated cells.