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Secretion of the amino-terminal fragment of the Hedgehog protein is necessary and sufficient for hedgehog signaling in Drosophila

journal contribution
posted on 2023-05-16, 09:42 authored by Fietz, MJ, Jacinto, A, Taylor, AM, Alexandre, C, Ingham, PW
Background: The Drosophila segment polarity gene hedgehog encodes a member of a family of secreted proteins that are involved in a variety of patterning processes, in both vertebrates and invertebrates. Some of these processes depend upon short-range or contact-dependent interactions, whereas others seem to involve long-range signalling. Two different models have been proposed to account for the execution of these contrasting processes by the same proteins: one postulates that Hedgehog acts exclusively over short distances, its long-range influences being effected through regulation of other signalling factors; the second postulates that different aspects of Hedgehog activity are mediated by distinct forms of the protein that are generated by autoproteolysis . Results: We have investigated these models by mutating the hedgehog coding region such that only the amino-terminal or carboxy-terminal half of the protein is secreted. Deletion of the carboxy-terminal portion has little effect on the signalling activity of the protein, whereas abolishing the secretion of the amino-terminal half leads to a complete loss of signalling. In addition, we find that increases in the level of expression within the normal hedgehog transcriptional domain of either the wild-type protein or the carboxy-terminal-deleted form expand the range of activity to a limited extent, but have only minor effects on cell identity. Conclusions: In Drosophila, all of the signalling activity of Hedgehog resides in the amino-terminal portion of the protein, the secretion of which is essential for its function. The range of Hedgehog is limited by the close association of the amino-terminal peptide with the cell surface but can be extended by elevating the level of its expression.

History

Publication title

Current Biology

Volume

5

Issue

6

Pagination

643-650

ISSN

0960-9822

Department/School

Tasmanian School of Medicine

Publisher

Cell Press

Place of publication

1100 Massachusetts Ave, Cambridge, USA, Ma, 02138

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the environmental sciences

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