Actin-based endosome and phagosome rocketing in macrophages: activation by the secretagogue antagonists lanthanum and zinc - PubMed (original) (raw)

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

Frederick S Southwick et al. Cell Motil Cytoskeleton. 2003 Jan.

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.

PubMed Disclaimer

Cited by

Leishmania donovani requires functional Cdc42 and Rac1 to prevent phagosomal maturation.
Lerm M, Holm A, Seiron A, Särndahl E, Magnusson KE, Rasmusson B. Lerm M, et al. Infect Immun. 2006 May;74(5):2613-8. doi: 10.1128/IAI.74.5.2613-2618.2006. Infect Immun. 2006. PMID: 16622197 Free PMC article.
Convergence of Ras- and Rac-regulated formin pathways is pivotal for phagosome formation and particle uptake in Dictyostelium.
Körber S, Junemann A, Litschko C, Winterhoff M, Faix J. Körber S, et al. Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2220825120. doi: 10.1073/pnas.2220825120. Epub 2023 Mar 10. Proc Natl Acad Sci U S A. 2023. PMID: 36897976 Free PMC article.
RhoA regulates peroxisome association to microtubules and the actin cytoskeleton.
Schollenberger L, Gronemeyer T, Huber CM, Lay D, Wiese S, Meyer HE, Warscheid B, Saffrich R, Peränen J, Gorgas K, Just WW. Schollenberger L, et al. PLoS One. 2010 Nov 8;5(11):e13886. doi: 10.1371/journal.pone.0013886. PLoS One. 2010. PMID: 21079737 Free PMC article.
Repeated cycles of rapid actin assembly and disassembly on epithelial cell phagosomes.
Yam PT, Theriot JA. Yam PT, et al. Mol Biol Cell. 2004 Dec;15(12):5647-58. doi: 10.1091/mbc.e04-06-0509. Epub 2004 Sep 29. Mol Biol Cell. 2004. PMID: 15456901 Free PMC article.
Live cell imaging of the assembly, disassembly, and actin cable-dependent movement of endosomes and actin patches in the budding yeast, Saccharomyces cerevisiae.
Huckaba TM, Gay AC, Pantalena LF, Yang HC, Pon LA. Huckaba TM, et al. J Cell Biol. 2004 Nov 8;167(3):519-30. doi: 10.1083/jcb.200404173. J Cell Biol. 2004. PMID: 15534003 Free PMC article.

Actin-based endosome and phagosome rocketing in macrophages: activation by the secretagogue antagonists lanthanum and zinc - PubMed (original) (raw)