Association of tetraspanin CD9 with transmembrane TGFα confers alterations in cell-surface presentation of TGFα and cytoskeletal organization

Imhof, Isabella; Gasper, Warren J.; Derynck, Rik

doi:10.1242/jcs.021717

Cited by 30 publications

(21 citation statements)

References 53 publications

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“…Thus, we hypothesized that the inactivity of Reck y72 is due to failure to reach the outer cell surface (see Simizu et al, 2005). We thus assayed the cell surface localization of epitope-tagged (3×FLAG and 2×HA) WT (Reck) and mutant (Reck y72 ) zebrafish proteins in non-permeabilized immunofluorescently stained cells (Imhof et al, 2008). In 293T cells epitope-tagged Reck was detected at the cell surface ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Reck enables cerebrovascular development by promoting canonical Wnt signaling

et al. 2015

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The cerebral vasculature provides the massive blood supply that the brain needs to grow and survive. By acquiring distinctive cellular and molecular characteristics it becomes the blood-brain barrier (BBB), a selectively permeable and protective interface between the brain and the peripheral circulation that maintains the extracellular milieu permissive for neuronal activity. Accordingly, there is great interest in uncovering the mechanisms that modulate the formation and differentiation of the brain vasculature. By performing a forward genetic screen in zebrafish we isolated no food for thought (nft y72 ), a recessive late-lethal mutant that lacks most of the intracerebral central arteries (CtAs), but not other brain blood vessels. We found that the cerebral vascularization deficit of nft y72 mutants is caused by an inactivating lesion in reversion-inducing cysteine-rich protein with Kazal motifs [reck; also known as suppressor of tumorigenicity 15 protein (ST15)], which encodes a membrane-anchored tumor suppressor glycoprotein. Our findings highlight Reck as a novel and pivotal modulator of the canonical Wnt signaling pathway that acts in endothelial cells to enable intracerebral vascularization and proper expression of molecular markers associated with BBB formation. Additional studies with cultured endothelial cells suggest that, in other contexts, Reck impacts vascular biology via the vascular endothelial growth factor (VEGF) cascade. Together, our findings have broad implications for both vascular and cancer biology.

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Section: Introductionmentioning

confidence: 99%

Reck enables cerebrovascular development by promoting canonical Wnt signaling

et al. 2015

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“…Among the membrane proteins that are functionally regulated by tetraspanins, there are several membrane-bound proteases, including ADAM10, ADAM17, MT-MMP1 (also known as MMP14) and the urokinase-type plasminogen activator Bass et al, 2005;Gutiérrez-López et al, 2011;Lafleur et al, 2009;Shiomi et al, 2005;Xu et al, 2009;Yañez-Mó et al, 2008), and several membrane-anchored growth factor precursors, such as transforming growth factor a (TGFa) or heparin-binding EGF-like growth factor (HBEGF) (Higashiyama et al, 1995;Imhof et al, 2008). In addition, several tetraspanins, in particular CD9, CD82 and CD151, associate with and/or modulate downstream signalling of tyrosine kinase receptors, including epithelial growth factor receptor (EGFR), ERBB2, c-MET and vascular endothelial growth factor receptor (VEGFR)-3 (also known as FLT4) (Franco et al, 2010;Iwasaki et al, 2013;Murayama et al, 2008;Novitskaya et al, 2014;Odintsova et al, 2003;Sridhar and Miranti, 2006;Takahashi et al, 2007).…”

Section: Regulation Of Membrane-anchored Enzymes and Growth Factor Simentioning

confidence: 99%

Tetraspanins at a glance

Charrin

Jouannet

Boucheix

et al. 2014

Journal of Cell Science

370

371

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Tetraspanins are a family of proteins with four transmembrane domains that play a role in many aspects of cell biology and physiology; they are also used by several pathogens for infection and regulate cancer progression. Many tetraspanins associate specifically and directly with a limited number of proteins, and also with other tetraspanins, thereby generating a hierarchical network of interactions. Through these interactions, tetraspanins are believed to have a role in cell and membrane compartmentalization. In this Cell Science at a Glance article and the accompanying poster, we describe the basic principles underlying tetraspaninbased assemblies and highlight examples of how tetraspanins regulate the trafficking and function of their partner proteins that are required for the normal development and function of several organs, including, in humans, the eye, the kidney and the immune system.

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“…The function of tetraspanins is diverse and not well understood in many cases but a common theme is the organization of membrane proteins into defined microdomains (Hemler 2005). They have been found in association not only with ADAMs ( particularly ADAM10), but also EGF ligands and the EGFR itself, suggesting that they may have complex influences on signaling (Imhof et al 2008;Murayama et al 2008).…”

Section: Tetraspanins: Spatial Control Of Adam Sheddingmentioning

confidence: 99%

“…In contrast, the tetraspanin CD9, which can bind to TACE and also to EGFR ligands, reduces shedding (Higashiyama et al 1995;Imhof et al 2008). By inhibiting ligand cleavage, tetraspanins may regulate switching from shedding to juxtamembrane signaling.…”

Section: Tetraspanins: Spatial Control Of Adam Sheddingmentioning

confidence: 99%

Regulation of Receptor Tyrosine Kinase Ligand Processing

Adrain

Freeman

2014

Cold Spring Harbor Perspectives in Biology

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A primary mode of regulating receptor tyrosine kinase (RTK) signaling is to control access of ligand to its receptor. Many RTK ligands are synthesized as transmembrane proteins. Frequently, the active ligand must be released from the membrane by proteolysis before signaling can occur. Here, we discuss RTK ligand shedding and describe the proteases that catalyze it in flies and mammals. We focus principally on the control of EGF receptor ligand shedding, but also refer to ligands of other RTKs. Two prominent themes emerge. First, control by regulated trafficking and cellular compartmentalization of the proteases and their ligand substrates plays a key role in shedding. Second, many external signals converge on the shedding proteases and their control machinery. Proteases therefore act as regulatory hubs that integrate information that the cell receives and translate it into precise outgoing signals. The activation of signaling by proteases is therefore an essential element of the cellular communication machinery.C ells must talk to one another. This principle applies throughout the tree of life: from unicellular bacteria, to the trillions of cells that coordinate to make a mammal. Communication between cells requires dedicated machinery, capable of relaying information across membranes. Transmembrane proteins are therefore essential for signaling. Understanding how this is regulated is paramount. In mammals, receptor tyrosine kinases (RTKs) and their ligands are important examples of such machinery (Schlessinger 2000), controlling many biological processes including development, immunity, tissue repair, and metabolic homeostasis (Ullrich and Schlessinger 1990). They are transmembrane proteins with an extracellular ligand-binding motif and an intracellular kinase domain. As discussed in other chapters, a common mode of RTK activation involves receptor dimerization induced by ligand binding (Lemmon and Schlessinger 2010).Regulated access of ligand to receptor, over distance and time, is key to controlling signaling. Ligands are frequently synthesized as transmembrane forms; when they remain membrane-tethered and cannot diffuse, the range over which they can operate is limited to adjacent cells (Massague and Pandiella 1993; Singh and 1 Present address: Instituto

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Association of tetraspanin CD9 with transmembrane TGFα confers alterations in cell-surface presentation of TGFα and cytoskeletal organization

Cited by 30 publications

References 53 publications

Reck enables cerebrovascular development by promoting canonical Wnt signaling

Reck enables cerebrovascular development by promoting canonical Wnt signaling

Tetraspanins at a glance

Regulation of Receptor Tyrosine Kinase Ligand Processing

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