Biomedical subjects

Fangliang Zhang

Publications and source records attributed to Fangliang Zhang.

3 recordsLinked to original sources

PubMed2005

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.g., elastic propulsion, elastic Brownian ratchet, tethered ratchet, and insertional polymerization models) requiring filament barbed ends to depart/detach from the motile object's surface during/after each monomer-addition step. Helical trajectories also explain why Listeria undergoes longitudinal-axis rotation on a length-scale matching the helical periodicity of Listeria's rocket tails.

Actins↗

PubMed2003

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. This treatment results in accentuated membrane ruffling and the formation of phagosomes and early endosomes that move rapidly through the cytoplasm by assembling actin filament rocket tails. Protein-specific immunolocalization demonstrated the presence of Arp2/3 complex in the polymerization zone and throughout the actin-rich tail, whereas N-WASP was most abundant in the polymerization zone. Although Arp2/3 and N-WASP play essential roles in nucleating filament assembly, other processes (i.e., elongation and filament cross-linking) are required to produce forces needed for motility. Efficient elongation was found to require zyxin, VASP, and profilin, proteins that interact by means of their ABM-1 and ABM-2 proline-rich motifs. The functional significance of these motifs was demonstrated by inhibition of vesicle motility by the motif-specific ABM-1 and ABM-2 analogues. Furthermore, lanthanum/zinc treatment also facilitated the early onset of actin-based vaccinia motility, a process that also utilizes Arp2/3 and N-WASP for nucleation and the zyxin-VASP-profilin complex for efficient elongation. Although earlier studies using cell extracts clouded the role of oligoproline sequences in activating the polymerization zone, our studies emphasize the importance of evaluating motility in living cells.

Actin-Related Protein 2↗

PubMed2002

Actin-based phagosome motility.

Despite abundant evidence of actin's involvement at the particle internalization stage of phagocytosis, little is known about whether phagosomes undergo the same type of actin-based motility as observed with endocytic vesicles or such intracellular pathogens as Listeria and Shigella. By employing video microscopy to follow the fate of latex bead-containing phagosomes within the cytoplasm of bone marrow macrophages, we have made the novel observation of actin-based phagosome motility. Immunofluorescence microscopy confirmed that phagosomes containing IgG-opsonized, bovine serum albumin (or BSA) -coated or uncoated latex beads all formed actin-rich rocket tails that persisted only during a brief, 1-2 min period of actin-based motility. Average speeds of actin-based phagosome motility were 0.13 +/- 0.06 microm/s for IgG-coated beads, 0.14 +/- 0.04 microm/s for BSA-coated beads, and 0.11+/- 0.03 microm/s for uncoated beads. Moreover, the speeds and motile-phase duration of each type of phagosome were comparable to the behavior of pinosomes [Merrifield et al., 1999: Nat. Cell Biol. 1:72-74.]. Determination of optimal conditions for observing and analyzing actin-based phagosome motility should facilitate future investigations of phagocytosis and phagosome maturation.

Actins↗