Identification of SH3 Domain Proteins Interacting with the Cytoplasmic Tail of the A Disintegrin and Metalloprotease 10 (ADAM10)

Ebsen, Henriette; Lettau, Marcus; Kabelitz, Dieter; Janßen, Ottmar

doi:10.1371/journal.pone.0102899

Cited by 31 publications

(23 citation statements)

References 75 publications

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“…The currently accepted model proposes that when cytosolic Ca 2+ concentration is increased, calmodulin and Ca 2+ interact, which dissociates calmodulin from pro-ADAM10, as its affinity is lower for the protease. ADAM10 hence becomes available for activation by furin and is eventually ready to process its own substrates [ 37 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

Pseudomonas aeruginosa ExlA and Serratia marcescens ShlA trigger cadherin cleavage by promoting calcium influx and ADAM10 activation

et al. 2017

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Pore-forming toxins are potent virulence factors secreted by a large array of bacteria. Here, we deciphered the action of ExlA from Pseudomonas aeruginosa and ShlA from Serratia marcescens on host cell-cell junctions. ExlA and ShlA are two members of a unique family of pore-forming toxins secreted by a two-component secretion system. Bacteria secreting either toxin induced an ExlA- or ShlA-dependent rapid cleavage of E-cadherin and VE-cadherin in epithelial and endothelial cells, respectively. Cadherin proteolysis was executed by ADAM10, a host cell transmembrane metalloprotease. ADAM10 activation is controlled in the host cell by cytosolic Ca2+ concentration. We show that Ca2+ influx, induced by ExlA or ShlA pore formation in the plasma membrane, triggered ADAM10 activation, thereby leading to cadherin cleavage. Our data suggest that ADAM10 is not a cellular receptor for ExlA and ShlA, further confirming that ADAM10 activation occurred via Ca2+ signalling. In conclusion, ExlA- and ShlA-secreting bacteria subvert a regulation mechanism of ADAM10 to activate cadherin shedding, inducing intercellular junction rupture, cell rounding and loss of tissue barrier integrity.

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Section: Resultsmentioning

confidence: 99%

Pseudomonas aeruginosa ExlA and Serratia marcescens ShlA trigger cadherin cleavage by promoting calcium influx and ADAM10 activation

et al. 2017

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“…Another laboratory [ 75 ] recently reported the identification of ADAM10-binding partners using a commercially available version of our SH3 domain library. They used a bacterially expressed version of the intracellular ADAM10 tail as a bait, and reported it to bind as many as 38 different SH3 domains.…”

Section: Discussionmentioning

confidence: 99%

“…More specifically, a defining feature of ADAMs that emerged from our studies was their ubiquitous binding to BAR and SH3 domain-containing proteins associated in actin regulation, protein sorting, vesicle transport, and endocytosis. In addition to two families of such proteins, namely SNXs and NADPH-organizers (which also contain a PX domain) that dominated our interaction screens, a third class of BAR and SH3-containing proteins, namely the PACSIN/endophilin family, has also been reported to bind to ADAMs [ 21 , 49 , 69 , 75 ]. SH3 domains from this family were also encountered in our screens, albeit at an inconclusively low frequency.…”

Section: Discussionmentioning

confidence: 99%

Preferred SH3 Domain Partners of ADAM Metalloproteases Include Shared and ADAM-Specific SH3 Interactions

et al. 2015

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A disintegrin and metalloproteinases (ADAMs) constitute a protein family essential for extracellular signaling and regulation of cell adhesion. Catalytic activity of ADAMs and their predicted potential for Src-homology 3 (SH3) domain binding show a strong correlation. Here we present a comprehensive characterization of SH3 binding capacity and preferences of the catalytically active ADAMs 8, 9, 10, 12, 15, 17, and 19. Our results revealed several novel interactions, and also confirmed many previously reported ones. Many of the identified SH3 interaction partners were shared by several ADAMs, whereas some were ADAM-specific. Most of the ADAM-interacting SH3 proteins were adapter proteins or kinases, typically associated with sorting and endocytosis. Novel SH3 interactions revealed in this study include TOCA1 and CIP4 as preferred partners of ADAM8, and RIMBP1 as a partner of ADAM19. Our results suggest that common as well as distinct mechanisms are involved in regulation and execution of ADAM signaling, and provide a useful framework for addressing the pathways that connect ADAMs to normal and aberrant cell behavior.

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“…Although numerous substrates have been identified, knowledge of the regulation of ADAM10 surface expression and proteolytic activity is still poor. According to one hypothesis the two processes are partly modulated by protein-protein interactions mediated by the intracellular portion of the protease (Ebsen et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

ADAM10 localization in temporomandibular joint disk with internal derangement: an ex vivo immunohistochemical study

et al. 2016

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Abstract:The purpose of this study was to determine the presence of ADAM10 in temporomandibular joint disk with internal derangement. Twentyfive paraffin blocks of displaced temporomandibular joint (TMJ) disk specimens from earlier investigations were retrieved from the archives of the University of Catania. Of these 16 had been removed from females and 9 from males; 11 with anterior disk displacement with reduction (ADDwR) and 14 with anterior disk displacement without reduction (ADDwoR). The sections were dehydrated, embedded in paraffin and cut. Then they were incubated in 0.3% H2O2/methanol and half of sections from each sample were incubated in diluted rabbit polyclonal anti-ADAM10 antibody. Then biotinylated antimouse/anti-rabbit IgG was applied to the sections, followed by avidin-biotinperioxidase complex. The results were analyzed and the results were that ADAM10 was overexpressed in the posterior band of sections from patients with ADDwR compared to the other bands of both ADDwR and ADDwoR sections. Overexpression correlated with severe histopathological degeneration. We believe these results have the potential to provide insights into the pathogenesis of TMJ disk degeneration and to help design new therapeutic approaches targeting the proteolytic events that lead to tissue degeneration. Early therapeutic block of ADAM10 activity could succeed in limiting aggrecan-rich matrix breakdown without affecting normal physiology.

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Identification of SH3 Domain Proteins Interacting with the Cytoplasmic Tail of the A Disintegrin and Metalloprotease 10 (ADAM10)

Cited by 31 publications

References 75 publications

Pseudomonas aeruginosa ExlA and Serratia marcescens ShlA trigger cadherin cleavage by promoting calcium influx and ADAM10 activation

Pseudomonas aeruginosa ExlA and Serratia marcescens ShlA trigger cadherin cleavage by promoting calcium influx and ADAM10 activation

Preferred SH3 Domain Partners of ADAM Metalloproteases Include Shared and ADAM-Specific SH3 Interactions

ADAM10 localization in temporomandibular joint disk with internal derangement: an ex vivo immunohistochemical study

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