Nitric oxide regulates endocytosis by S-nitrosylation of dynamin

Gaofeng Wang, Nader H. Moniri, Kentaro Ozawa, Jonathan S. Stamler, Yehia Daaka

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

The GTPase dynamin regulates endocytic vesicle budding from the plasma membrane, but the molecular mechanisms involved remain incompletely understood. We report that dynamin, which interacts with NO synthase, is S-nitrosylated at a single cysteine residue (C607) after stimulation of the β2 adrenergic receptor. S-nitrosylation increases dynamin self-assembly and GTPase activity and facilitates its redistribution to the membrane. A mutant protein bearing a C607A substitution does not self-assemble properly or increase its enzymatic activity in response to NO. In NO-generating cells, expression of dynamin C607A, like the GTPase-deficient dominant-negative K44A dynamin, inhibits both β2 adrenergic receptor internalization and bacterial invasion. Furthermore, exogenous or endogenously produced NO enhances internalization of both β2 adrenergic and epidermal growth factor receptors. Thus, NO regulates endocytic vesicle budding by S-nitrosylation of dynamin. Collectively, our data suggest a general NO-dependent mechanism by which the trafficking of receptors may be regulated and raise the idea that pathogenic microbes and viruses may induce S-nitrosylation of dynamin to facilitate cellular entry.

Original languageEnglish
Pages (from-to)1295-1300
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number5
DOIs
StatePublished - Jan 31 2006
Externally publishedYes

Fingerprint

Dynamins
Endocytosis
Nitric Oxide
GTP Phosphohydrolases
Transport Vesicles
Adrenergic Receptors
Mutant Proteins
Nitric Oxide Synthase
Adrenergic Agents
Cysteine
Cell Membrane
Viruses
Membranes

Keywords

  • Infection
  • Protein-protein interaction
  • Receptor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Nitric oxide regulates endocytosis by S-nitrosylation of dynamin. / Wang, Gaofeng; Moniri, Nader H.; Ozawa, Kentaro; Stamler, Jonathan S.; Daaka, Yehia.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 5, 31.01.2006, p. 1295-1300.

Research output: Contribution to journalArticle

Wang, Gaofeng ; Moniri, Nader H. ; Ozawa, Kentaro ; Stamler, Jonathan S. ; Daaka, Yehia. / Nitric oxide regulates endocytosis by S-nitrosylation of dynamin. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 5. pp. 1295-1300.
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