Polarized secretion of Drosophila EGFR ligand from photoreceptor neurons is controlled by ER localization of the ligand-processing machinery

Autor: Eyal D. Schejter, Shaul Yogev, Ben-Zion Shilo
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Cell signaling
QH301-705.5
Cell Biology/Neuronal Signaling Mechanisms
Recombinant Fusion Proteins
Axon terminus
Endosomes
Biology
Endoplasmic Reticulum
Ligands
Cell Biology/Cell Signaling
General Biochemistry
Genetics and Molecular Biology
Developmental Biology/Molecular Development
Cell Biology/Membranes and Sorting
Epidermal growth factor
Cell polarity
Animals
Drosophila Proteins
Protein Isoforms
Secretion
Biology (General)
Epidermal Growth Factor
General Immunology and Microbiology
Developmental Biology/Morphogenesis and Cell Biology
General Neuroscience
Rhomboid
Endoplasmic reticulum
Cell Polarity
Membrane Proteins
Cell biology
Developmental Biology/Neurodevelopment
ErbB Receptors
Drosophila melanogaster
nervous system
Developmental Biology/Cell Differentiation
Photoreceptor Cells
Invertebrate
Signal transduction
General Agricultural and Biological Sciences
Research Article
Signal Transduction
Zdroj: PLoS Biology, Vol 8, Iss 10 (2010)
PLoS Biology
ISSN: 1545-7885
1544-9173
Popis: Trafficking within the endoplasmic reticulum and specialized localization of the intra-membrane protease Rhomboid regulate EGF ligand-dependent signaling in Drosophila photoreceptor axon termini.
The release of signaling molecules from neurons must be regulated, to accommodate their highly polarized structure. In the developing Drosophila visual system, photoreceptor neurons secrete the epidermal growth factor receptor ligand Spitz (Spi) from their cell bodies, as well as from their axonal termini. Here we show that subcellular localization of Rhomboid proteases, which process Spi, determines the site of Spi release from neurons. Endoplasmic reticulum (ER) localization of Rhomboid 3 is essential for its ability to promote Spi secretion from axons, but not from cell bodies. We demonstrate that the ER extends throughout photoreceptor axons, and show that this feature facilitates the trafficking of the Spi precursor, the ligand chaperone Star, and Rhomboid 3 to axonal termini. Following this trafficking step, secretion from the axons is regulated in a manner similar to secretion from cell bodies. These findings uncover a role for the ER in trafficking proteins from the neuronal cell body to axon terminus.
Author Summary Cells secrete signaling molecules that trigger a variety of responses in neighboring cells by activating their respective cell-surface receptors. Because many cells in an organism are polarized, regulating the precise location of ligand secretion is important for controlling the position and nature of the response. During the development of the compound eye of the fruit fly Drosophila, for example, a ligand of the epidermal growth factor family called Spitz (Spi) is secreted from both the apical and basal (axonal) poles of photoreceptor cells but with different outcomes. Photoreceptor cells are recruited to the developing eye following apical secretion of Spi. Conversely, basal secretion of this same ligand, at a significant distance from the cell body, triggers differentiation of cells in the outer layer of the brain. Although secretion of Spi is known to occur at both poles of the cell, one important question is how Spi and its processing machinery are trafficked throughout the length of the photoreceptor axon to achieve basal secretion. In this study we show that the key to axonal trafficking is the regulated localization of Spi and its processing machinery, including the intramembrane protease Rhomboid, to sites within the endoplasmic reticulum (ER), which extends along the length of the axon. Two different Rhomboid proteins are expressed in photoreceptor cells, but only one of them is localized to the ER. We show that this ER-localized Rhomboid is indeed necessary and sufficient for Spi processing at axon termini. Our work therefore demonstrates how variations in intracellular localization of conserved signaling components can alter signaling outcomes dramatically. It also highlights the importance of the ER in trafficking proteins along the axon.
Databáze: OpenAIRE
Externí odkaz: