Dynamin 2 Is Required for Phagocytosis in Macrophages

doi:10.1084/jem.190.12.1849

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© 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

Original Article

Dynamin 2 Is Required for Phagocytosis in Macrophages

Elizabeth S. Gold^a,b, David M. Underhill^a, Naomi S. Morrissette^a, Jian Guo^a, Mark A. McNiven^c, and Alan Aderem^a
^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

Correspondence to: Alan Aderem, Department of Immunology, Box 357650, 1959 N.E. Pacific Ave., Seattle, WA 98195. Tel:206-616-5045 Fax:206-616-7237 E-mail:aaderem{at}u.washington.edu.

Cells internalize soluble ligands through endocytosis and largeparticles through actin-based phagocytosis. The dynamin familyof GTPases mediates the scission of endocytic vesicles fromthe plasma membrane. We report here that dynamin 2, a ubiquitouslyexpressed dynamin isoform, has a role in phagocytosis in macrophages.Dynamin 2 is enriched on early phagosomes, and expression ofa dominant-negative mutant of dynamin 2 significantly inhibitsparticle internalization at the stage of membrane extensionaround the particle. This arrest in phagocytosis resembles thatseen with inhibitors of phosphoinositide 3-kinase (PI3K), andinhibition of PI3K prevents the recruitment of dynamin to thesite of particle binding. Although expression of mutant dynaminin macrophages inhibited particle internalization, it had noeffect on the production of inflammatory mediators elicitedby particle binding.

Key Words: phagocytosis, macrophages, dynamin, inflammation, phosphoinositide3-kinase

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