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A membrane-targeting signal in the amino terminus of the neuronal protein GAP-43

Nature volume 341, pages 345–348 (1989)Cite this article

Abstract

NEURONS and other cells, such as those of epithelia, accumulate particular proteins in spatially discrete domains of the plasma membrane. This enrichment is probably important for localization of function, but it is not clear how it is accomplished. One proposal for epithelial cells is that proteins contain targeting signals which guide preferential accumulation in basal or apical membranes1. The growth-cone membrane of a neuron serves as a specialized transduction system, which helps to convert cues from its environment into regulated growth. Because it can be physically separated from the cell soma, it has been possible to show that the growth-cone membrane contains a restricted set of total cellular proteins2, although, to our knowledge, no proteins are limited to that structure. One of the most prominent proteins in the growth-cone membrane is GAP-43 (refs 3–5; for reviews see refs 6 and 7). Basi et al. have suggested that the N-terminus of GAP-43 might be important for the binding of GAP-43 to the growth-cone membrane8. Skene and Virag9 recently found that the cysteines in the N-terminus are fatty-acylated and that this post-translational modification correlates with membrane-binding ability. We investigated the binding of GAP-43 to the growth-cone membrane by mutational analysis and by laser-scanning confocal microscopy of fusion proteins that included regions of GAP-43 and chloram-phenicol acetyltransferase (CAT). We found that a short stretch of the GAP-43 N-terminus suffices to direct accumulation in growth-cone membranes, especially in the filopodia. This supports a previous proposal8,9 for the importance of this region of GAP-43 in determining the membrane distribution of GAP-43.

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Authors and Affiliations

  1. Developmental Biology Laboratory of the Massachusetts General Hospital Cancer Center, Departments of Medicine and Neurology of Harvard Medical School,

    Mauricio X. Zuber, Stephen M. Strittmatter & Mark C. Fishman

  2. the Howard Hughes Medical Institute, Wellman 4, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA

    Mauricio X. Zuber, Stephen M. Strittmatter & Mark C. Fishman

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  1. Mauricio X. Zuber
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  2. Stephen M. Strittmatter
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  3. Mark C. Fishman
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Zuber, M., Strittmatter, S. & Fishman, M. A membrane-targeting signal in the amino terminus of the neuronal protein GAP-43. Nature 341, 345–348 (1989). https://doi.org/10.1038/341345a0

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