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

Frederick S. Southwick, Wei Li, Fangliang Zhang, William L. Zeile, Daniel L. Purich

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)41-55
Number of pages15
JournalCell Motility and the Cytoskeleton
Volume54
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

Lanthanum
Phagosomes
Macrophage Activation
Endosomes
Zyxin
Polymerization
Profilins
Zinc
Actins
Actin-Related Protein 2-3 Complex
Vaccinia
Transport Vesicles
Locomotion
Cell Extracts
Actin Cytoskeleton
Proline
Organelles
Cytoplasm
Bone Marrow
Macrophages

ASJC Scopus subject areas

  • Cell Biology

Cite this

Actin-based endosome and phagosome rocketing in macrophages : Activation by the secretagogue antagonists lanthanum and zinc. / Southwick, Frederick S.; Li, Wei; Zhang, Fangliang; Zeile, William L.; Purich, Daniel L.

In: Cell Motility and the Cytoskeleton, Vol. 54, No. 1, 01.01.2003, p. 41-55.

Research output: Contribution to journalArticle

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