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Alzheimer's disease is a neurodegenerative condition believed to be initiated by production of amyloid-beta peptide, which leads to synaptic dysfunction and progressive memory loss. Using a mouse model of Alzheimer's disease (3xTg-AD), an 8-arm radial maze was employed to assess spatial working memory. Unexpectedly, the younger (3month old) 3xTg-AD mice were as impaired in the spatial working memory task as the older (8month old) 3xTg-AD mice when compared with age-matched NonTg control animals. Field potential recordings from the CA1 region of slices prepared from the ventral hippocampus were obtained to assess synaptic transmission and capability for synaptic plasticity. At 3months of age, the NMDA receptor-dependent component of LTP was reduced in 3xTg-AD mice. However, the magnitude of the non-NMDA receptor-dependent component of LTP was concomitantly increased, resulting in a similar amount of total LTP in 3xTg-AD and NonTg mice. At 8months of age, the NMDA receptor-dependent LTP was again reduced in 3xTg-AD mice, but now the non-NMDA receptor-dependent component was decreased as well, resulting in a significantly reduced total amount of LTP in 3xTg-AD compared with NonTg mice. Both 3 and 8month old 3xTg-AD mice exhibited reductions in paired-pulse facilitation and NMDA receptor-dependent LTP that coincided with the deficit in spatial working memory. The early presence of this cognitive impairment and the associated alterations in synaptic plasticity demonstrate that the onset of some behavioral and neurophysiological consequences can occur before the detectable presence of plaques and tangles in the 3xTg-AD mouse model of Alzheimer's disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The Dictyostelium discoideum 34-kDa protein is an F-actin bundling protein that demonstrates diverse distributions in the cell during cell shape changes and cell movement. The protein is expressed at a very low level in the amoeba, just 0.4% of the total cell protein. This presents a challenging problem when purifying sufficient protein for structural and biochemical studies. The purification procedure is lengthy and yields only a few milligrams of protein. An alternative protein expression system, that of the bacterial T7 expression system, was used to produce large quantities of recombinant 34-kDa protein (r34-kDa). The soluble r34-kDa protein constitutes up to a quarter of the total bacterial protein, and was purified to homogeneity by a modification of the purification procedure for the native D. discoideum 34-kDa protein (N34-kDa). The r34-kDa possesses all the same functional characteristics as the N34-kDa protein with respect to its interactions with F-actin in vitro: it bound to and cross-linked F-actin, mediated F-actin bundle formation, directly bound calcium, and demonstrated calcium-sensitive F-actin binding activities.

The cellular organization, function, and molecular composition of selected biological systems with prominent actin filament bundles are reviewed. An overall picture of the great variety of functions served by actin bundles emerges from this overview. A unifying theme is that the actin cross-linking proteins are conserved throughout the eukaryotic kingdom and yet assembled in a variety of combinations to produce actin bundles of differing functions. Mechanisms of actin bundle formation in vitro are considered illustrating the variety of physical and chemical driving forces in this exceedingly complex process. Our limited knowledge regarding the formation of actin filament bundles in vivo is contrasted with the elegant biophysical studies performed in vitro but nonetheless reveals that interactions with membranes, nucleation sites, and other organizational components must contribute to formation of actin bundles in vivo.