Cortactin: Cell Functions of A Multifaceted Actin-Binding Protein

Schnoor, Michael; Stradal, Theresia E. B.; Rottner, Klemens

doi:10.1016/j.tcb.2017.10.009

Cited by 154 publications

(169 citation statements)

References 164 publications

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“…7). Actin-binding proteins such as cortactin regulate bone resorption and vesicular trafficking (48,49). We previously reported that inhibition of Pmepa1 expression decreased cell surface expression of RANK in POCs (25), suggesting that Pmepa1 also plays a role in vesicular transport.…”

Section: Discussionmentioning

confidence: 99%

Prostate transmembrane protein androgen induced 1 is induced by activation of osteoclasts and regulates bone resorption

Hirata

Shiraki

et al. 2018

FASEB j.

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Osteoclasts derived from hematopoietic cells are activated on bone surface. To resorb bone, osteoclasts release acid and lysosome acid hydrolase via membrane transport. Prostate transmembrane protein androgen induced 1 (Pmepa1) is a type I transmembrane protein that regulates proliferation, migration, and metastasis of cancer cells. Because recent reports showed that Pmepa1 is involved in membrane transport in cancer cells, we investigated the role of Pmepa1 in osteoclast function. Pmepa1 expression was barely detected in osteoclasts formed on plastic surfaces in vitro, but was markedly increased in activated osteoclasts formed on calcified matrix. Inhibitors of bone resorption, such as alendronate, bafilomycin A1, and the PI3K inhibitor LY294002, suppressed the expression of Pmepa1 in osteoclasts. Knockdown of Pmepa1 expression impaired bone resorption activity and inhibited formation of a ring‐like, actin‐rich podosome belt that is essential for osteoclast function. Pmepa1 protein localized to lysosomes in osteoclasts. In addition, in sites of bone destruction observed in rats with adjuvant‐induced arthritis, a marked high level of Pmepa1 expression was associated with the osteoclasts' resorbing bone. Our results suggest that Pmepa1 is a critical regulator of bone resorption and is a promising marker for activated osteoclasts and a potential therapeutic target in pathologic bone destruction.—Xu, X., Hirata, H., Shiraki, M., Kamohara, A., Nishioka, K., Miyamoto, H., Kukita, T., Kukita, A. Prostate transmembrane protein androgen induced 1 is induced by activation of osteoclasts and regulates bone resorption. FASEB J. 33, 4365–4375 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Prostate transmembrane protein androgen induced 1 is induced by activation of osteoclasts and regulates bone resorption

Hirata

Shiraki

et al. 2018

FASEB j.

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“…The results are representative of three independent experiments c-Src kinase (Bays & DeMali, 2017;Critchley, 2004;Schnoor, Stradal, & Rottner, 2018;. In fact, tyrosine phosphorylation of both signalling factors is commonly controlled by the FIGURE 5 Overexpression of human integrin-β 1 in AZ-521 cells does not restore CagA translocation by Helicobacter pylori.…”

Section: Mkn45 Caco2 or Other Ceacam-expressing Gastrointestinal Cementioning

confidence: 99%

Expression of CEACAM1 or CEACAM5 in AZ-521 cells restores the type IV secretion deficiency for translocation of CagA byHelicobacter pylori

Tegtmeyer

Harrer

Schmitt

et al. 2018

Cellular Microbiology

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Helicobacter pylori represents an important pathogen involved in diseases ranging from gastritis, peptic ulceration, to gastric malignancies. Prominent virulence factors comprise the vacuolating cytotoxin VacA and the cytotoxin-associated genes pathogenicity island (cagPAI)-encoded type IV secretion system (T4SS). The T4SS effector protein CagA can be translocated into AGS and other gastric epithelial cells followed by phosphorylation through c-Src and c-Abl tyrosin kinases to hijack signalling networks. The duodenal cell line AZ-521 has been recently introduced as novel model system to investigate CagA delivery and phosphorylation in a VacA-dependent fashion. In contrast, we discovered that AZ-521 cells display a T4SS incompetence phenotype for CagA injection, which represents the first reported gastrointestinal cell line with a remarkable T4SS defect. We proposed that this deficiency may be due to an imbalanced coexpression of T4SS receptor integrin-β 1 or carcinoembryonic antigenrelated cell adhesion molecules (CEACAMs), which were described recently as novel H. pylori receptors. We demonstrate that AZ-521 cells readily express integrin-β 1 , but overexpression of integrin-β 1 constructs did not restore the T4SS defect. We further show that AZ-521 cells lack the expression of CEACAMs. We demonstrate that genetic introduction of either CEACAM1 or CEACAM5, but not CEACAM6, in AZ-521 cells is sufficient to permit injection and phosphorylation of CagA by H. pylori to degrees observed in the AGS cell model. Expression of CEACAM1 or CEACAM5 in infected AZ-521 cells was also accompanied by tyrosine dephosphorylation of the cytoskeletal proteins vinculin and cortactin, a hallmark of H. pylori-infected AGS cells.Our results suggest the existence of an integrin-β 1and CEACAM1-or CEACAM5dependent T4SS delivery pathway for CagA, which is clearly independent of VacA.The presence of two essential host protein receptors during infection with H. pylori represents a unique feature in the bacterial T4SS world. Further detailed investigation of these T4SS functions will help to better understand infection strategies by bacterial pathogens.

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“…Finally, the expression of truncated cortactin proteins decreases the efficiency of tsVSV-G export from the TGN towards the cell surface. Cortactin promotes the formation of branched actin polymers through interactions with the Arp2/3 complex [96], and dynamin 2 is a small GTPase essential for membrane fission [97]. These findings show the importance of Arf1 in the recruitment of an actin/cortactin/dynamin 2 complex essential for post-Golgi transport.…”

Section: Arf1 Positive Tubular Carriersmentioning

confidence: 80%

Direct trafficking pathways from the Golgi apparatus to the plasma membrane

Stalder

Gershlick

2020

Seminars in Cell & Developmental Biology

102

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In eukaryotic cells, protein sorting is a highly regulated mechanism important for many physiological events. After synthesis in the endoplasmic reticulum and trafficking to the Golgi apparatus, proteins sort to many different cellular destinations including the endolysosomal system and the extracellular space. Secreted proteins need to be delivered directly to the cell surface. Sorting of secreted proteins from the Golgi apparatus has been a topic of interest for over thirty years, yet there is still no clear understanding of the machinery that forms the post-Golgi carriers. Most evidence points to these post-Golgi carriers being tubular pleomorphic structures that bud from the trans-face of the Golgi. In this review, we present the background studies and highlight the key components of this pathway, we then discuss the machinery implicated in the formation of these carriers, their translocation across the cytosol, and their fusion at the plasma membrane.Abbreviations: ATP, adenosine triphosphate; BFA, Brefeldin A; CARTS, CARriers of the TGN to the cell Surface; CI-MPR, cation-independent mannose-6 phosphate receptor; CtBP3/BARS, C-terminus binding protein 3/BFA adenosine diphosphate-ribosylated substrate; ER, endoplasmic reticulum; GlcCer, glucosylceramide; PAUF, pancreatic adenocarcinoma up-regulated factor; PM, plasma membrane; RUSH, retention using selective hooks; SBP, streptavidin-binding peptide; SM, sphingomyelin; SNARE, soluble N-ethylmaleimide sensitive fusion protein attachment protein receptor;SPCA1, secretory pathway calcium ATPase 1; TGN, trans-Golgi Network; TIRF, total internal reflection fluorescence; ts, temperature sensitive; VSV, vesicular stomatitis virus J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f

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Cortactin: Cell Functions of A Multifaceted Actin-Binding Protein

Cited by 154 publications

References 164 publications

Prostate transmembrane protein androgen induced 1 is induced by activation of osteoclasts and regulates bone resorption

Prostate transmembrane protein androgen induced 1 is induced by activation of osteoclasts and regulates bone resorption

Expression of CEACAM1 or CEACAM5 in AZ-521 cells restores the type IV secretion deficiency for translocation of CagA byHelicobacter pylori

Direct trafficking pathways from the Golgi apparatus to the plasma membrane

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