A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal

Sandra Isenmann, Yeesim Khew-Goodall, Jennifer Gamble, Mathew Vadas, Binks W. Wattenberg

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Screening of a library derived from primary human endothelial cells revealed a novel human isoform of vesicle-associated membrane protein-1 (VAMP-1), a protein involved in the targeting and/or fusion of transport vesicles to their target membrane. We have termed this novel isoform VAMP-1B and designated the previously described isoform VAMP-1A. VAMP-1B appears to be an alternatively spliced form of VAMP-1. A similar rat splice variant of VAMP-1 (also termed VAMP-1B) has recently been reported. Five different cultured cell lines, from different lineages, all contained VAMP-1B but little or no detectable VAMP-1A mRNA, as assessed by PCR. In contrast, brain mRNA contained VAMP-1A but no VAMP-1B. The VAMP-1B sequence encodes a protein identical to VAMP-1A except for the carboxy-terminal five amino acids. VAMP- 1 is anchored in the vesicle membrane by a carboxy-terminal hydrophobic sequence. In VAMP-1A the hydrophobic anchor is followed by a single threonine, which is the carboxy-terminal amino acid. In VAMP-1B the predicted hydrophobic membrane anchor is shortened by four amino acids, and the hydrophobic sequence is immediately followed by three charged amino acids, arginine-arginine-aspartic acid. Transfection of human endothelial cells with epitope-tagged VAMP-1B demonstrated that VAMP-1B was targeted to mitochondria whereas VAMP-1A was localized to the plasma membrane and endosome-like structures. Analysis of C-terminal mutations of VAMP-1B demonstrated that mitochondrial targeting depends both on the addition of positive charge at the C terminus and a shortened hydrophobic membrane anchor. These data suggest that mitochondria may be integrated, at least at a mechanistic level, to the vesicular trafficking pathways that govern protein movement between other organelles of the cell.

LanguageEnglish
Pages1649-1660
Number of pages12
JournalMolecular Biology of the Cell
Volume9
Issue number7
Publication statusPublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Isenmann, S., Khew-Goodall, Y., Gamble, J., Vadas, M., & Wattenberg, B. W. (1998). A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal. Molecular Biology of the Cell, 9(7), 1649-1660.
Isenmann, Sandra ; Khew-Goodall, Yeesim ; Gamble, Jennifer ; Vadas, Mathew ; Wattenberg, Binks W. / A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal. In: Molecular Biology of the Cell. 1998 ; Vol. 9, No. 7. pp. 1649-1660.
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Isenmann, S, Khew-Goodall, Y, Gamble, J, Vadas, M & Wattenberg, BW 1998, 'A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal', Molecular Biology of the Cell, vol. 9, no. 7, pp. 1649-1660.

A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal. / Isenmann, Sandra; Khew-Goodall, Yeesim; Gamble, Jennifer; Vadas, Mathew; Wattenberg, Binks W.

In: Molecular Biology of the Cell, Vol. 9, No. 7, 1998, p. 1649-1660.

Research output: Contribution to journalArticle

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