© The Rockefeller University Press, 0022-1007/1999/12/1849/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 12, December 20, 1999 1849-1856
Dynamin 2 Is Required for Phagocytosis in Macrophages
Elizabeth S. Golda,b,
David M. Underhilla,
Naomi S. Morrissettea,
Jian Guoa,
Mark A. McNivenc, and
Alan Aderema
a Department of Immunology, University of Washington, Seattle, Washington 98195
b Division of Cardiology, University of Washington, Seattle, Washington 98195
c Department of Biochemistry and Molecular Biology, The Center for Basic Research in Digestive Diseases, Mayo Foundation, Rochester, Minnesota 55905
Department of Immunology, Box 357650, 1959 N.E. Pacific Ave., Seattle, WA 98195.206-616-7237206-616-5045
aaderem{at}u.washington.edu
Cells internalize soluble ligands through endocytosis and large particles through actin-based phagocytosis. The dynamin family of GTPases mediates the scission of endocytic vesicles from the plasma membrane. We report here that dynamin 2, a ubiquitously expressed dynamin isoform, has a role in phagocytosis in macrophages. Dynamin 2 is enriched on early phagosomes, and expression of a dominant-negative mutant of dynamin 2 significantly inhibits particle internalization at the stage of membrane extension around the particle. This arrest in phagocytosis resembles that seen with inhibitors of phosphoinositide 3-kinase (PI3K), and inhibition of PI3K prevents the recruitment of dynamin to the site of particle binding. Although expression of mutant dynamin in macrophages inhibited particle internalization, it had no effect on the production of inflammatory mediators elicited by particle binding.
Key Words: phagocytosis macrophages dynamin inflammation phosphoinositide 3-kinase
Abbreviations used in this paper: eGFP, enhanced GFP; GFP, green fluorescent protein; LDL, low-density lipoprotein; PI3K, phosphoinositide 3-kinase; RP, resident peritoneal; SH, Src homology; TGN, trans-Golgi network; TRITC, tetramethyl rhodamine isothiocyanate.
© 1999 The Rockefeller University Press

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-
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-
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-
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-
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-
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[Abstract]
[Full Text]
-
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[Abstract]
[Full Text]
-
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[Abstract]
[Full Text]
-
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168: 2415-2423
[Abstract]
[Full Text]
-
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99: 161-166
[Abstract]
[Full Text]
-
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99: 167-172
[Abstract]
[Full Text]
-
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276: 48458-48465
[Abstract]
[Full Text]
-
May, R., Machesky, L.
(2001). Phagocytosis and the actin cytoskeleton. J. Cell Sci.
114: 1061-1077
[Abstract]
-
McNiven, M. A., Kim, L., Krueger, E. W., Orth, J. D., Cao, H., Wong, T. W.
(2000). Regulated Interactions between Dynamin and the Actin-Binding Protein Cortactin Modulate Cell Shape. JCB
151: 187-198
[Abstract]
[Full Text]
-
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(2000). A Functional Link between Dynamin and the Actin Cytoskeleton at Podosomes. JCB
150: 377-390
[Abstract]
[Full Text]
-
Cao, H, Thompson, H., Krueger, E., McNiven, M.
(2000). Disruption of Golgi structure and function in mammalian cells expressing a mutant dynamin. J. Cell Sci.
113: 1993-2002
[Abstract]
-
Naga Prasad, S. V., Barak, L. S., Rapacciuolo, A., Caron, M. G., Rockman, H. A.
(2001). Agonist-dependent Recruitment of Phosphoinositide 3-Kinase to the Membrane by beta -Adrenergic Receptor Kinase 1. A ROLE IN RECEPTOR SEQUESTRATION. J. Biol. Chem.
276: 18953-18959
[Abstract]
[Full Text]