Reduced purine biosynthesis in humans after their divergence from Neandertals.

We analyze the metabolomes of humans, chimpanzees, and macaques in muscle, kidney and three different regions of the brain. Although several compounds in amino acid metabolism occur at either higher or lower concentrations in humans than in the other primates, metabolites downstream of adenylosuccinate lyase, which catalyzes two reactions in purine synthesis, occur at lower concentrations in humans. This enzyme carries an amino acid substitution that is present in all humans today but absent in Neandertals.

Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase.

The availability of genomic data from extinct homini such as Neanderthals has caused a revolution in palaeontology allowing the identification of modern human-specific protein substitutions. Currently, little is known as to how these substitutions alter the proteins on a molecular level. Here, we investigate adenylosuccinate lyase, a conserved enzyme involved in purine metabolism for which several substitutions in the modern human protein (hADSL) have been described to affect intelligence and behaviour.

Deep and precise quantification of the mouse synaptosomal proteome reveals substantial remodeling during postnatal maturation.

During postnatal murine maturation, behavioral patterns emerge and become shaped by experience-dependent adaptations. During the same period, the morphology of dendritic spines, the morphological correlates of excitatory synapses, is known to change, and there is evidence of concurrent alterations of the synaptosomal protein machinery. To obtain comprehensive and quantitative insights in the developmental regulation of the proteome of synapses, we prepared cortical synaptosomal fractions from a total of 16 individual juvenile and adult mouse brains (age 3 or 8 weeks, respectively).

Dynamics of dendritic spines in the mouse auditory cortex during memory formation and memory recall.

Long-lasting changes in synaptic connections induced by relevant experiences are believed to represent the physical correlate of memories. Here, we combined chronic in vivo two-photon imaging of dendritic spines with auditory-cued classical conditioning to test if the formation of a fear memory is associated with structural changes of synapses in the mouse auditory cortex. We find that paired conditioning and unpaired conditioning induce a transient increase in spine formation or spine elimination, respectively.

Co-evolution-driven switch of J-protein specificity towards an Hsp70 partner.

Molecular mechanisms by which protein-protein interactions are preserved or lost after gene duplication are not understood. Taking advantage of the well-studied yeast mtHsp70:J-protein molecular chaperone system, we considered whether changes in partner proteins accompanied specialization of gene duplicates. Here, we report that existence of the Hsp70 Ssq1, which arose by duplication of the gene encoding multifunction mtHsp70 and specializes in iron-sulphur cluster biogenesis, correlates with functional and structural changes in the J domain of its J-protein partner Jac1.