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Macrophage podosomes assemble at the leading lamella by growth and fragmentation.

Evans JG, Correia I, Krasavina O, Watson N, Matsudaira P - J. Cell Biol. (2003)

Bottom Line: The large podosome cluster precursor also appears to be an adhesion structure; it contains actin, fimbrin, integrin, and is in close apposition to the substratum.Microtubule inhibitors paclitaxel and demecolcine inhibit the turnover and polarized formation of podosomes, but not the turnover rate of actin in these structures.Because daughter podosomes and podosome cluster precursors are preferentially located at the leading edge, they may play a critical role in continually generating new sites of cell adhesion.

View Article: PubMed Central - PubMed

Affiliation: BioImaging Center, Cambridge, MA 02142, USA. jgevans@wi.mit.edu

ABSTRACT
Podosomes are actin- and fimbrin-containing adhesions at the leading edge of macrophages. In cells transfected with beta-actin-ECFP and L-fimbrin-EYFP, quantitative four-dimensional microscopy of podosome assembly shows that new adhesions arise at the cell periphery by one of two mechanisms; de novo podosome assembly, or fission of a precursor podosome into daughter podosomes. The large podosome cluster precursor also appears to be an adhesion structure; it contains actin, fimbrin, integrin, and is in close apposition to the substratum. Microtubule inhibitors paclitaxel and demecolcine inhibit the turnover and polarized formation of podosomes, but not the turnover rate of actin in these structures. Because daughter podosomes and podosome cluster precursors are preferentially located at the leading edge, they may play a critical role in continually generating new sites of cell adhesion.

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A model for podosome assembly. Podosome assembly and disassembly takes place within an adhesion-rich zone. At the leading edge of the lamella, a podosome assembles de novo and disassembles in a microtubule-independent process. Podosome lifetime can be extended in a microtubule-dependent process by fission into daughter podosomes, fusion with another podosome, or growth into a PCP and fission into a podosome cluster. The assembly of daughter podosomes keeps pace with the leading lamella, whereas the mother podosome remains stationary until disassembling at the rear of the adhesion zone.
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fig5: A model for podosome assembly. Podosome assembly and disassembly takes place within an adhesion-rich zone. At the leading edge of the lamella, a podosome assembles de novo and disassembles in a microtubule-independent process. Podosome lifetime can be extended in a microtubule-dependent process by fission into daughter podosomes, fusion with another podosome, or growth into a PCP and fission into a podosome cluster. The assembly of daughter podosomes keeps pace with the leading lamella, whereas the mother podosome remains stationary until disassembling at the rear of the adhesion zone.

Mentions: To provide a framework for understanding podosome dynamics, we have developed a model for the assembly and turnover of podosomes (Fig. 5). At the leading edge, podosomes assemble de novo and are stabilized in a microtubule-dependent manner leading to fusion with a neighboring podosome, fission into daughter podosomes, or more dramatically, growth into a PCP and fission into a podosome cluster (Fig. 4). Not only is the PCP a novel adhesion-related structure, but repeated fusion and fission of podosomes is also a novel mode of behavior for nonmembrane-bound supramolecular structures. These processes supply new podosomes at the leading edge of the cell as it advances. The significance of this non-de novo assembly mechanism may be the ability of podosomes to transfer tension from an existing site to a nascent site, thus pulling the lamella forward as the leading edge extends.


Macrophage podosomes assemble at the leading lamella by growth and fragmentation.

Evans JG, Correia I, Krasavina O, Watson N, Matsudaira P - J. Cell Biol. (2003)

A model for podosome assembly. Podosome assembly and disassembly takes place within an adhesion-rich zone. At the leading edge of the lamella, a podosome assembles de novo and disassembles in a microtubule-independent process. Podosome lifetime can be extended in a microtubule-dependent process by fission into daughter podosomes, fusion with another podosome, or growth into a PCP and fission into a podosome cluster. The assembly of daughter podosomes keeps pace with the leading lamella, whereas the mother podosome remains stationary until disassembling at the rear of the adhesion zone.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199349&req=5

fig5: A model for podosome assembly. Podosome assembly and disassembly takes place within an adhesion-rich zone. At the leading edge of the lamella, a podosome assembles de novo and disassembles in a microtubule-independent process. Podosome lifetime can be extended in a microtubule-dependent process by fission into daughter podosomes, fusion with another podosome, or growth into a PCP and fission into a podosome cluster. The assembly of daughter podosomes keeps pace with the leading lamella, whereas the mother podosome remains stationary until disassembling at the rear of the adhesion zone.
Mentions: To provide a framework for understanding podosome dynamics, we have developed a model for the assembly and turnover of podosomes (Fig. 5). At the leading edge, podosomes assemble de novo and are stabilized in a microtubule-dependent manner leading to fusion with a neighboring podosome, fission into daughter podosomes, or more dramatically, growth into a PCP and fission into a podosome cluster (Fig. 4). Not only is the PCP a novel adhesion-related structure, but repeated fusion and fission of podosomes is also a novel mode of behavior for nonmembrane-bound supramolecular structures. These processes supply new podosomes at the leading edge of the cell as it advances. The significance of this non-de novo assembly mechanism may be the ability of podosomes to transfer tension from an existing site to a nascent site, thus pulling the lamella forward as the leading edge extends.

Bottom Line: The large podosome cluster precursor also appears to be an adhesion structure; it contains actin, fimbrin, integrin, and is in close apposition to the substratum.Microtubule inhibitors paclitaxel and demecolcine inhibit the turnover and polarized formation of podosomes, but not the turnover rate of actin in these structures.Because daughter podosomes and podosome cluster precursors are preferentially located at the leading edge, they may play a critical role in continually generating new sites of cell adhesion.

View Article: PubMed Central - PubMed

Affiliation: BioImaging Center, Cambridge, MA 02142, USA. jgevans@wi.mit.edu

ABSTRACT
Podosomes are actin- and fimbrin-containing adhesions at the leading edge of macrophages. In cells transfected with beta-actin-ECFP and L-fimbrin-EYFP, quantitative four-dimensional microscopy of podosome assembly shows that new adhesions arise at the cell periphery by one of two mechanisms; de novo podosome assembly, or fission of a precursor podosome into daughter podosomes. The large podosome cluster precursor also appears to be an adhesion structure; it contains actin, fimbrin, integrin, and is in close apposition to the substratum. Microtubule inhibitors paclitaxel and demecolcine inhibit the turnover and polarized formation of podosomes, but not the turnover rate of actin in these structures. Because daughter podosomes and podosome cluster precursors are preferentially located at the leading edge, they may play a critical role in continually generating new sites of cell adhesion.

Show MeSH
Related in: MedlinePlus