Exocytotic fusion is activated by Rab3a peptides

Andres Oberhauser, Jonathan R. Monck, William E. Balch, Julio M. Fernandez

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

STUDIES of intracellular traffic in yeast and mammalian systems have implicated members of the Rab family of small GTP-binding proteins as regulators of membrane fusion1-10. We have used the patch clamp technique to measure exocytotic fusion events directly and investigate the role of GTP-binding proteins in regulating exocytosis in mast cells. Intracellular perfusion of mast cells with GTP-γS is sufficient to trigger complete exocytotic degranulation in the absence of other intracellular messengers11. Here we show that GTP is a potent inhibitor of GTP-γS-induced degranulation, indicating that sustained activation of a GTP-binding protein is sufficient for membrane fusion. We have found that synthetic oligopeptides, corresponding to part of the effector domain of Rab3a12, stimulate complete exocytotic degranulation, similar to that induced by GTP-γS. The response is selective for Rab3a sequence and is strictly dependent on Mg2+ and ATP. This suggests that sustained activation of a Rab3 protein causes exocytotic fusion. The peptide response can be accelerated by GDP-βS, suggesting that Rab3a peptides compete with endogenous Rab3 proteins for a binding site on a target effector protein, which causes fusion on activation.

Original languageEnglish (US)
Pages (from-to)270-273
Number of pages4
JournalNature
Volume360
Issue number6401
StatePublished - Nov 19 1992
Externally publishedYes

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Guanosine Triphosphate
rab3 GTP-Binding Proteins
Peptides
GTP-Binding Proteins
Mast Cells
GTP-Binding Protein Regulators
Oligopeptides
Membrane Fusion
Exocytosis
Patch-Clamp Techniques
Protein Binding
Perfusion
Adenosine Triphosphate
Yeasts
Binding Sites
Membranes
Proteins

ASJC Scopus subject areas

  • General

Cite this

Oberhauser, A., Monck, J. R., Balch, W. E., & Fernandez, J. M. (1992). Exocytotic fusion is activated by Rab3a peptides. Nature, 360(6401), 270-273.

Exocytotic fusion is activated by Rab3a peptides. / Oberhauser, Andres; Monck, Jonathan R.; Balch, William E.; Fernandez, Julio M.

In: Nature, Vol. 360, No. 6401, 19.11.1992, p. 270-273.

Research output: Contribution to journalArticle

Oberhauser, A, Monck, JR, Balch, WE & Fernandez, JM 1992, 'Exocytotic fusion is activated by Rab3a peptides', Nature, vol. 360, no. 6401, pp. 270-273.
Oberhauser A, Monck JR, Balch WE, Fernandez JM. Exocytotic fusion is activated by Rab3a peptides. Nature. 1992 Nov 19;360(6401):270-273.
Oberhauser, Andres ; Monck, Jonathan R. ; Balch, William E. ; Fernandez, Julio M. / Exocytotic fusion is activated by Rab3a peptides. In: Nature. 1992 ; Vol. 360, No. 6401. pp. 270-273.
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