Target size of the ryanodine receptor from junctional terminal cisternae of sarcoplasmic reticulum

Target inactivation analysis was carried out on the ryanodine receptor. This receptor recently has been implicated as the channel involved in the calcium release process in excitation-contraction coupling and was localized to the junctional terminal cisternae of sarcoplasmic reticulum from skeletal muscle [Fleischer, S., Ogunbunmi, E. M., Dixon, M. C., & Fleer, E.A.M. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7256-7259]. Irradiation of the junctional terminal cisternae resulted in an exponential decrease in ryanodine binding with radiation dose, thereby consistent with target theory. The target molecular weight was found to be 138,000 +/- 21,000, i.e., smaller than the polypeptide that binds ryanodine. The calcium pump protein in the same membrane preparation served as an internal control to validate the methodology.     

"An ape's view of the Oldowan" revisited

In 1989, Wynn and McGrew published an explicit comparison between Oldowan technology and what was then known of chimpanzee technology. They compared the range and variety of tools, adaptive role of tools, carrying distances, spatial cognition, manufacturing procedures, and modes of learning. They concluded that everything archeologists had reconstructed about the behavior of Oldowan hominins could be accommodated within the ape adaptive grade; that is, a paraphyletic group united by overall similarities in anatomy and, in this case, behavior. The only Oldowan activities that were almost unknown for modern apes were the long-distance transport of objects and direct competition with carnivores, which was implied by meat acquisition activities. "In its general features Oldowan culture was ape, not human. Nowhere in this picture need we posit elements such as language, extensive sharing, division of labor, or pair-bonded families, all of which are part of the baggage carried by the term human."     

Identification of residues important for DNA binding in the full-length human Rad52 protein

Human Rad52 (HsRad52) is a DNA-binding protein (418 residues) that promotes the catalysis of DNA double strand break repair by the Rad51 recombinase. HsRad52 self-associates to form ring-shaped oligomers as well as higher order complexes of these rings. Analysis of the structural and functional organization of protein domains suggests that many of the determinants of DNA binding lie within the N-terminal 85 residues. Crystal structures of two truncation mutants, HsRad52(1-212) and HsRad52(1-209) support the idea that this region makes up an important part of the DNA binding domain. Here, we report the results of saturating alanine scanning mutagenesis of the N-terminal domain of full-length HsRad52 in which we identify residues that are likely involved in direct contact with single-stranded DNA (ssDNA). Our results largely agree with the position of side-chains seen in the crystal structures but also suggest that certain DNA binding and cross-subunit interactions differ between the 11 subunit ring in the crystal structures of the truncation mutant proteins versus the seven subunit ring formed by full-length HsRad52.     

Random assembly of SUR subunits in KATP channel complexes

Sulfonylurea receptors (SURs) associate with Kir6.x subunits to form tetradimeric KATP channel complexes. SUR1 and SUR2 confer differential channel sensitivities to nucleotides and pharmacological agents, and are expressed in specific, but overlapping, tissues. This raises the question of whether these different SUR subtypes can assemble in the same channel complex and generate channels with hybrid properties. To test this, we engineered dimeric constructs of wild type or N160D mutant Kir6.2 fused to SUR1 or SUR2A. Dimeric fusions formed functional, ATP-sensitive, channels. Coexpression of weakly rectifying SUR1-Kir6.2 (WTF-1) with strongly rectifying SUR1-Kir6.2[N160D] (NDF-1) in COSm6 cells results in mixed subunit complexes that exhibit unique rectification properties. Coexpression of NDF-1 and SUR2A-Kir6.2 (WTF-2) results in similar complex rectification, reflecting the presence of SUR1- and SUR2A-containing dimers in the same channel. The data demonstrate clearly that SUR1 and SUR2A subunits associate randomly, and suggest that heteromeric channels will occur in native tissues.     

IMP dehydrogenase type 1 associates with polyribosomes translating rhodopsin mRNA

IMP dehydrogenase (IMPDH) catalyzes the pivotal step in guanine nucleotide biosynthesis. Here we show that both IMPDH type 1 (IMPDH1) and IMPDH type 2 are associated with polyribosomes, suggesting that these housekeeping proteins have an unanticipated role in translation regulation. This interaction is mediated by the subdomain, a region of disputed function that is the site of mutations that cause retinal degeneration. The retinal isoforms of IMPDH1 also associate with polyribosomes. The most common disease-causing mutation, D226N, disrupts the polyribosome association of at least one retinal IMPDH1 isoform. Finally, we find that IMPDH1 is associated with polyribosomes containing rhodopsin mRNA. Because any perturbation of rhodopsin expression can trigger apoptosis in photoreceptor cells, these observations suggest a likely pathological mechanism for IMPDH1-mediated hereditary blindness. We propose that IMPDH coordinates the translation of a set of mRNAs, perhaps by modulating localization or degradation.     

Kinji Imanishi and 60 years of Japanese primatology

On December 3^rd, 1948, only three years after the Second World War, Kinji Imanishi (1902–1992) went to Koshima island to study the wild Japanese monkeys. Imanishi was flanked by two young students, Jun'ichiro Itani (1926–2002) and Shunzo Kawamura (1924–2003). This year, 2008, is thus the 60^th anniversary of the founding of primatology in Japan.     

The nature of culture: technological variation in chimpanzee predation on army ants revisited

Chimpanzee (Pan troglodytes) predation on army ants (Dorylus, subgenus Anomma) is an impressive example of skillful use of elementary technology, and it has been suggested to reflect cultural differences among chimpanzee communities. Alternatively, the observed geographic diversity in army-ant-eating may represent local behavioral responses of the chimpanzees to the anti-predator traits of the army ant species present at the different sites. We examined assemblages of available prey species, their behavior and morphology, consumption by chimpanzees, techniques employed, and tool lengths at 14 sites in eastern, central, and western Africa. Where army ants are eaten, tool length and concomitant technique are a function of prey type. Epigaeically foraging species with aggressive workers that inflict painful bites are harvested with longer tools and usually by the "pull-through" technique; species foraging in leaf-litter with less aggressive workers that inflict less painful bites are harvested with short tools and by the "direct-mouthing" technique. However, prey species characteristics do not explain several differences in army-ant-eating between Bossou (Guinea) and Ta? (Ivory Coast), where the same suite of prey species is available and is consumed. Moreover, the absence of army-ant-eating at five sites cannot be explained by the identity of available prey species, as all the species found at these sites are eaten elsewhere. We conclude that some of the observed variation in the predator-prey relationship of chimpanzees and army ants reflects environmental influences driven by the prey, while other variation is not linked to prey characteristics and may be solely sociocultural.