Distinct Roles for N-Ethylmaleimide-sensitive Fusion Protein (NSF) Suggested by the Identification of a Second Drosophila NSF Homolog

doi:10.1074/jbc.270.32.18742

Distinct Roles for N-Ethylmaleimide-sensitive Fusion Protein (NSF) Suggested by the Identification of a Second Drosophila NSF Homolog (*)

From the (1) Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706,
(2) Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721,
(3) Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143, and
(4) Molecular Biology Unit, Tata Institute of Fundamental Research, Bombay 400005, India

Abstract

The N-ethylmaleimide-sensitive fusion protein (NSF) is a cytoplasmic protein implicated in the fusion of intracellular transport vesicles with their target membranes. NSF is thought to function in the fusion of essentially all types of vesicles, including endoplasmic reticulum, Golgi, and endocytic vesicles, as well as secretory vesicles undergoing regulated fusion (for review see Rothman, J. E.(1994) Nature 372, 55-63). However, little [Medline] experimental evidence exists to address the possibility that organisms might have multiple NSF proteins serving distinct functions in the same or different cells. We previously cloned a neurally expressed Drosophila homolog, dNSF-1 (Ordway, R. W., Pallanck, L., and Ganetzky, B.(1994) Proc. Natl. Acad. Sci. U. S. A. 91, 5715-5719), and have subsequently identified mutations in this gene that confer an apparent failure of synaptic transmission at elevated temperature (Pallanck, L., Ordway, R. W., and Ganetzky, B.(1995) Nature, 376, 25; Siddiqi, O., and Benzer, S.(1976) Proc. Natl. Acad. Sci. U. S. A. 73, 3253-3257). Here we report that 1) Drosophila contains a second NSF homolog, termed dNSF-2, that exhibits 84% amino acid identity to dNSF-1, 2) dNSF-1 and dNSF-2 display overlapping but different temporal expression, and 3) multiple transcripts are derived from the dNSF-2 gene. These findings raise the possibility that different NSF gene products serve distinct or overlapping functions within the organism.

Footnotes

↵* This work was supported by National Institutes of Health Grant NS5927 (to Regis B. Kelly), American Cancer Society Fellowship 3985 (to L. P.), National Institutes of Health Fellowship NS09364 (to R. W. O.), Department of Science and Technology of the Government of India Grant DST/SP-SO N11/92 (to K. S. K. and M. R.), and National Institutes of Health Grant NS15390 and a McKnight fellowship (to B. G.). This is Paper 3435 from the Laboratory of Genetics, University of Wisconsin, Madison. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank®/EMBL Data Bank with accession number(s) U09373[GenBank].
↵¹ The abbreviations used are:

NSF

N-ethylmaleimide-sensitive fusion protein

SNAP

soluble NSF attachment protein

SNARE

SNAP receptor

PCR

polymerase chain reaction

kb

kilobase(s)

dNSF

Drosophila NSF.
- Received May 18, 1995.
- Revision received June 16, 1995.