Calmodulin-binding domains in Alzheimer's disease proteins: extending the calcium hypothesis

The calcium hypothesis of Alzheimer's disease (AD) invokes the disruption of calcium signaling as the underlying cause of neuronal dysfunction and ultimately apoptosis. As a primary calcium signal transducer, calmodulin (CaM) responds to cytosolic calcium fluxes by binding to and regulating the activity of target CaM-binding proteins (CaMBPs). Ca(2+)-dependent CaMBPs primarily contain domains (CaMBDs) that can be classified into motifs based upon variations on the basic amphiphilic alpha-helix domain involving conserved hydrophobic residues at positions 1-10, 1-14 or 1-16. In contrast, an IQ or IQ-like domain often mediates Ca(2+)-independent CaM-binding. Based on these attributes, a search for CaMBDs reveals that many of the proteins intimately linked to AD may be calmodulin-binding proteins, opening new avenues for research on this devastating disease.     

α-Mannosidase and Microcyst Differentiation in the Cellular Slime Mold Polysphondylium pallidum

The intracellular and extracellular pattern of α-mannosidase (EC 3.2.1.24) activity was studied during microcyst differentiation in the cellular slime mold, Polysphondylium pallidum. The evidence suggests that microcyst differentiation requires continuous protein synthesis. α-Mannosidase activity is present in amoebae and increases with differentiation, and the data indicate that this increase in activity requires concurrent protein synthesis. The enzyme is excreted during the differentiation process, and the release of the enzyme is not stopped by cycloheximide. A cystless mutant does not show the normal intracellular pattern of α-mannosidase but does excrete the enzyme. Microcyst differentiation is proposed as an alternative system to multicellular slime mold development for the biochemical analysis of certain aspects of cellular differentiation.     

Ca and cell fusion during sexual development in liquid cultures of Dictyostelium discoideum

Cell fusion resulting in zygote giant cell formation is the first observable event of sexual development in D. discoideum. The results reported here show that this process is Ca²⁺-dependent and that by increasing the level of Ca²⁺ in the medium the number of cell fusions can be increased 57-fold over control cultures. The data also suggest that Ca²⁺ has both an early and late function in the development of zygotes and these functions are mediated at the cell surface. These results plus the availability of a liquid culture for generating large volumes of cells make sexual development in D. discoideum an excellent system for the analysis of membrane fusion in eukaryotes.     

Calmodulin‐mediated events during the life cycle of the amoebozoan Dictyostelium discoideum

This review focusses on the functions of intracellular and extracellular calmodulin, its target proteins and their binding proteins during the asexual life cycle of Dictyostelium discoideum. Calmodulin is a primary regulatory protein of calcium signal transduction that functions throughout all stages. During growth, it mediates autophagy, the cell cycle, folic acid chemotaxis, phagocytosis, and other functions. During mitosis, specific calmodulin‐binding proteins translocate to alternative locations. Translocation of at least one cell adhesion protein is calmodulin dependent. When starved, cells undergo calmodulin‐dependent chemotaxis to cyclic AMP generating a multicellular pseudoplasmodium. Calmodulin‐dependent signalling within the slug sets up a defined pattern and polarity that sets the stage for the final events of morphogenesis and cell differentiation. Transected slugs undergo calmodulin‐dependent transdifferentiation to re‐establish the disrupted pattern and polarity. Calmodulin function is critical for stalk cell differentiation but also functions in spore formation, events that begin in the pseudoplasmodium. The asexual life cycle restarts with the calmodulin‐dependent germination of spores. Specific calmodulin‐binding proteins as well as some of their binding partners have been linked to each of these events. The functions of extracellular calmodulin during growth and development are also discussed. This overview brings to the forefront the central role of calmodulin, working through its numerous binding proteins, as a primary downstream regulator of the critical calcium signalling pathways that have been well established in this model eukaryote. This is the first time the function of calmodulin and its target proteins have been documented through the complete life cycle of any eukaryote.     

Sources of fish in the ephemeral western iishana region of the Cuvelai–Etosha Basin in Angola and Namibia

The triangle between the Kavango and Kunene rivers is drained by the Cuvelai, an ephemeral and deltaic drainage system covering more than 100 000 km². In good rainfall years, the area becomes populated by fish communities dominated by five species migrating southward towards the endorheic Etosha Pan, the basin’s terminal sump. When water dries up, fish subsequently die-off and their sudden appearance in rainy years has captivated scientists for decades. The current study was prompted by hitherto untapped indigenous knowledge through narratives of opportunistic fish harvesting of migrating fish at temporary connections between the Kunene River and the Cuvelai- Etosha Basin. A reconnaissance fish survey in 2017 was complemented by digital satellite images and elevation data analyses. Results support the presence of at least three major ephemeral fish migration routes. The dominant fish genera migrating upstream in Kunene tributaries comprise Enteromius, Oreochromis and Clarias, all eurytopic and known to undertake upstream, lateral and downstream migrations on floodplains. Although other notable fish refugia in the Cuvelai–Etosha Basin are yet to be identified, there is a necessity for the protection and management of these migration routes in tandem with studies on the nature and extent of this inter-basin fish migration under climate change and variability.     

THE FUSION OF SEXUAL NUCLEI

A classification scheme is proposed for the types of sexual nuclear fusion that occur in eukaryotes. The two main classes are envelope fusion and envelope vesiculation and each is further divided into subclasses. The formation of sexual nuclei (pronuclei) has been detailed in representatives from various phyla, but is best understood in animals, in which the development of male and female pronuclei differs in some respects. The only characterized cytoplasmic mediator of pronuclear movement are microtubules. Groups of eukaryotes can be classified according to the type of nuclear fusion they reveal. Envelope fusion occurs in animals whose eggs are fertilized at the pronuclear stage, and in all plants, fungi, protozoa and algae studied to date. Ultrastructural details of envelope fusion have shown variations that are classified in our scheme as direct and indirect, the latter being restricted to the plant kingdom. Envelope vesiculation only occurs in animals, in which it is the most common means of nuclear fusion. Four subclasses can be defined according to the timing of the vesiculation of the nuclear envelopes, and the extent of envelope surface projections prior to fusion. The amount of work reported on the controlling mechanisms of nuclear fusion has been limited, but some evidence of genetic control has been provided, particularly in fungi. Evidence is presented to indicate that the control of the fusion competence of nuclei is a negative one. This review of the information available on nuclear fusion points out the need for extensive future comparative studies if this important process is to be better understood.     

The molecular organization of the beta-globin complex of the deer mouse, Peromyscus maniculatus

Recombinant DNA clones have been isolated that contain 80 kb of the beta-globin complex from the deer mouse, Peromyscus maniculatus. Comparisons of this complex with that from the laboratory mouse, Mus domesticus (with an order 5'-Hbby, Hbb-bhO, Hbb-bhl, Hbb-bh2, Hbb-bh3, Hbb-bl, Hbb-b2 3') highlight organizational trends in the beta-globin complex since the two species diverged. Unlike other mammals studied thus far, the deer mouse possesses three adult genes. Partial sequence analysis indicates that each of the three adult genes is intact and hence may be functional. Hybridization of one of the two Mus pseudogenes, Hbb-bh3, to genomic blots from Peromyscus reveals that it has a homologous counterpart in Peromyscus. Homologous genes to the two gamma-like Mus genes, Hbb-bhO and Hbb-bhl, are also found in Peromyscus. The strong hybridization between the Hbb-bhl genes and significant nucleotide similarity between the Hbb-bhO genes suggest that both pairs are important for the ontogeny of these mice although no known product has been identified for the Hbb-bhO genes. The presence of Hbb-bhO and Hbb-bhl in Peromyscus suggests that the duplication that created this related gene set occurred before the two lineages diverged. A single gene for Hbb-y has been isolated from Peromyscus. The adult region in Peromyscus has undergone significant divergence from the same region in Mus, having three rather than two adult genes, the acquisition of at least 15 kb of extra DNA relative to Mus, and possibly the loss of the Hbb-bh2 pseudogene. The nonadult region of the complex, in contrast, contains the same set of genes apparently distributed over the same amount of DNA as in the Mus beta- globin complex. This observation suggests that the embryonic region of the complex is more evolutionarily stable than the adult region.