Maternal phenylketonuria syndrome: studies in mice suggest a potential approach to a continuing problem.

BackgroundUntreated phenylketonuria (PKU), one of the most common human genetic disorders, usually results in mental retardation. Although a protein-restricted artificial diet can prevent retardation, dietary compliance in adults is often poor. In pregnant PKU women, noncompliance can result in maternal PKU syndrome, where high phenylalanine (Phe) levels cause severe fetal complications.

Partial rescue of neuropathology in the murine model of PKU following administration of recombinant phenylalanine ammonia lyase (pegvaliase).

Pegylated recombinant phenylalanine ammonia lyase (pegvaliase) is an enzyme substitution therapy being evaluated for the treatment of phenylketonuria (PKU). PKU is characterized by elevated plasma phenylalanine, which is thought to lead to a deficiency in monoamine neurotransmitters and ultimately, neurocognitive dysfunction. A natural history evaluation in a mouse model of PKU demonstrated a profound decrease in tyrosine hydroxylase (TH) immunoreactivity in several brain regions, beginning at 4weeks of age.

Guidance of actin filament elongation on filament-binding tracks.

Biomolecular motors, which convert chemical energy into mechanical work in intracellular processes, have high potential in bionanotechnology in vitro as molecular shuttles or nanoscale actuators. In this context, guided elongation of actin filaments in vitro could be used to lay tracks for myosin motor-based shuttles or to direct nanoscale actuators based on actin filament end-tracking motors. To guide the direction of filament polymerization on surfaces, microcontact printing was used to create tracks of chemically modified myosin, which binds to, but cannot exert force on, filaments.

Listeria's right-handed helical rocket-tail trajectories: mechanistic implications for force generation in actin-based motility.

Listeria monocytogenes forms right-handed helical rocket tail trajectories during actin-based motility in cell-free extracts, and this stereochemical feature is consistent with actoclampin's affinity-modulated, clamped-filament elongation model [Dickinson and Purich, 2002: Biophys J 82:605-617]. In that mechanism, right-handed torque is generated by an end-tracking molecular motor, each comprised of a filament barbed end and clamping protein that processively traces the right-handed helix of its filament partner. By contrast, torque is not a predicted property of those models (e.

Actin-based endosome and phagosome rocketing in macrophages: activation by the secretagogue antagonists lanthanum and zinc.

Although motile endocytic vesicles form actin-rich rocket tails [Merrifield et al., 1999: Nature Cell Biol 1:72-74], the mechanism of intracellular organelle locomotion remains poorly understood. We now demonstrate that bone marrow macrophages treated with lanthanum and zinc ions, well-known secretagogue antagonists, reliably exhibit vesicle motility.