scholarly journals Membrane capacitance recordings resolve dynamics and complexity of receptor-mediated endocytosis in Wnt signalling

2018 ◽  
Author(s):  
Vera Bandmann ◽  
Ann Schirin Mirsanaye ◽  
Johanna Schäfer ◽  
Gerhard Thiel ◽  
Thomas Holstein ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Intracellular Signaling ◽  
Wnt Signaling Pathway ◽  
Membrane Capacitance ◽  
Hek293 Cells ◽  
Receptor Mediated Endocytosis ◽  
Wnt Ligands ◽  
Endocytic Vesicles ◽  
Kinetics Of

AbstractReceptor-mediated endocytosis is an essential process in signaling pathways for an activation of intracellular signaling cascades. One example is the Wnt signaling pathway, which seems to depend on endocytosis of the ligand-receptor complex for initiation of Wnt signal transduction. So far, the role of different endocytic pathways in Wnt signaling, the molecular players and the kinetics of this process are unclear. Here, we monitor endocytosis in Wnt3a and Wnt5a mediated signaling by membrane capacitance recordings of HEK293 cells. Our measurements revealed a fast and substantial increase in the number of endocytic vesicles. This endocytotic activity is specifically elicited by extracellular Wnt ligands; it starts immediately upon ligand binding and ceases over a period of ten minutes. By using specific inhibitors, we can dissect Wnt induced endocytosis into two independent pathways, where canonical Wnt3a is taken up mainly by clathrin-independent endocytosis and Wnt5a exclusively by clathrin-mediated endocytosis.

scholarly journals Membrane capacitance recordings resolve dynamics and complexity of receptor-mediated endocytosis in Wnt signalling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Vera Bandmann ◽  
Ann Schirin Mirsanaye ◽  
Johanna Schäfer ◽  
Gerhard Thiel ◽  
Thomas Holstein ◽  
...  
Keyword(s):  
Wnt Signalling ◽  
Membrane Capacitance ◽  
Hek293 Cells ◽  
Signalling Pathways ◽  
Receptor Mediated Endocytosis ◽  
Cellular Processes ◽  
Wnt Ligands ◽  
Endocytic Vesicles ◽  
Kinetics Of ◽  
Wnt Signal

Abstract Receptor-mediated endocytosis is an essential process in signalling pathways for activation of intracellular signalling cascades. One example is the Wnt signalling pathway that seems to depend on endocytosis of the ligand-receptor complex for initiation of Wnt signal transduction. To date, the roles of different endocytic pathways in Wnt signalling, molecular players and the kinetics of the process remain unclear. Here, we monitored endocytosis in Wnt3a and Wnt5a-mediated signalling with membrane capacitance recordings of HEK293 cells. Our measurements revealed a swift and substantial increase in the number of endocytic vesicles. Extracellular Wnt ligands specifically triggered endocytotic activity, which started immediately upon ligand binding and ceased within a period of ten minutes. By using specific inhibitors, we were able to separate Wnt-induced endocytosis into two independent pathways. We demonstrate that canonical Wnt3a is taken up mainly by clathrin-independent endocytosis whereas noncanonical Wnt5a is exclusively regulated via clathrin-mediated endocytosis. Our findings show that membrane capacitance recordings allow the resolution of complex cellular processes in plasma membrane signalling pathways in great detail.

THE ROLE OF AGONISTS AND ANTAGONISTS OF THE WNT SIGNALING PATHWAY IN PATIENTS WITH ANDROGENIC ALOPECIA AND ALOPECIA AREATA

2021 ◽  
pp. 87-95
Author(s):  
Samoylova A.V. ◽  
Snimshchikova I.A. ◽  
Plotnikova M.O. ◽  
Yakushkina N.Y.
Keyword(s):  
Wnt Signaling ◽  
Hair Follicle ◽  
Signaling Pathway ◽  
Alopecia Areata ◽  
Intracellular Signaling ◽  
Wnt Signaling Pathway ◽  
Follicle Cells ◽  
Androgenic Alopecia ◽  
Active Population

Alopecia is a common pathology among the active population, which leads not only to cosmetic defects, but also to the development of somatic diseases against the background of traumatic effects and chronic stress. The pathogenetic mechanisms of hair follicle formation are complex and diverse, since numerous factors, including the components of the Wnt signaling pathway, have an effect on its morphogenesis, the study of which is the subject of this study. The search for possible early markers of the development of alopecia led to interest in the study of the main morphogenic proteins of WNT - the signaling pathway (one of the intracellular signaling pathways, which control the development of blood vessels, as well as the growth and division of hair follicle cells) sclerostin and β-catenin among patients with androgenic and alopecia areata. The article presents data on the quantitative content of β-catenin and sclerostin in the blood serum in patients with androgenic and alopecia areata. Their possible pathways of complex interaction and influence on the morphogenesis of the hair follicle and the activity of the Wnt-signaling pathway have been analyzed, and the relationship between changes in the level of morphogenic proteins of the WNT-signaling pathway with sex and the course of the disease has been described. Establishment of the prognostic role of morphogenic proteins of the WNT signaling pathway in androgenic and alopecia areata will allow not only identify the personal risk of disease progression and to determine approaches to targeted therapy, but to develop and introduce updated diagnostic screening into dermatological practice.

scholarly journals WNT Signaling in Melanoma

2020 ◽  
Vol 21 (14) ◽  
pp. 4852 ◽  
Author(s):  
Anna Gajos-Michniewicz ◽  
Malgorzata Czyz
Keyword(s):  
Wnt Signaling ◽  
Planar Cell Polarity ◽  
Wnt Signaling Pathway ◽  
Adult Life ◽  
Canonical Pathway ◽  
Current View ◽  
Directional Growth ◽  
Wide Range ◽  
Wnt Ligands

WNT-signaling controls important cellular processes throughout embryonic development and adult life, so any deregulation of this signaling can result in a wide range of pathologies, including cancer. WNT-signaling is classified into two categories: β-catenin-dependent signaling (canonical pathway) and β-catenin-independent signaling (non-canonical pathway), the latter can be further divided into WNT/planar cell polarity (PCP) and calcium pathways. WNT ligands are considered as unique directional growth factors that contribute to both cell proliferation and polarity. Origin of cancer can be diverse and therefore tissue-specific differences can be found in WNT-signaling between cancers, including specific mutations contributing to cancer development. This review focuses on the role of the WNT-signaling pathway in melanoma. The current view on the role of WNT-signaling in cancer immunity as well as a short summary of WNT pathway-related drugs under investigation are also provided.

scholarly journals The Role of Canonical Wnt Signaling in Regulating Radioresistance

2018 ◽  
Vol 48 (2) ◽  
pp. 419-432 ◽  
Author(s):  
Yuanyuan Zhao ◽  
Leilei Tao ◽  
Jun Yi ◽  
Haizhu Song ◽  
Longbang Chen
Keyword(s):  
Wnt Signaling ◽  
Cancer Progression ◽  
Wnt Signaling Pathway ◽  
Growth Factor Receptor ◽  
Cancer Resistance ◽  
Canonical Wnt Signaling ◽  
Damage Repair ◽  
Epidermal Growth ◽  
Canonical Wnt

Radioresistance is a major obstacle in radiotherapy for cancer, and strategies are needed to overcome this problem. Currently, radiotherapy combined with targeted therapy such as inhibitors of phosphoinosotide 3-kinase/Akt and epidermal growth factor receptor signaling have become the focus of studies on radiosensitization. Apart from these two signaling pathways, which promote radioresistance, deregulation of Wnt signaling is also associated with the radioresistance of multiple cancers. Wnts, as important messengers in the tumor microenvironment, are involved in cancer progression mainly via canonical Wnt signaling. Their role in promoting DNA damage repair and inhibiting apoptosis facilitates cancer resistance to radiation. Thus, it seems reasonable to target Wnt signaling as a method for overcoming radioresistance. Many small-molecule inhibitors that target the Wnt signaling pathway have been identified and shown to promote radiosensitization. Therefore, a Wnt signaling inhibitor may help to overcome radioresistance in cancer therapy.

scholarly journals Wnt Signaling in Vascular Calcification

2021 ◽  
Vol 8 ◽  
Author(s):  
Kaylee Bundy ◽  
Jada Boone ◽  
C. LaShan Simpson
Keyword(s):  
Cardiovascular Disease ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Vascular Calcification ◽  
Arterial Wall ◽  
Wnt Signaling Pathway ◽  
Phenotypic Switch ◽  
Wnt Ligands ◽  
And Function ◽  
Canonical Wnt

Cardiovascular disease is a worldwide epidemic and considered the leading cause of death globally. Due to its high mortality rates, it is imperative to study the underlying causes and mechanisms of the disease. Vascular calcification, or the buildup of hydroxyapatite within the arterial wall, is one of the greatest contributors to cardiovascular disease. Medial vascular calcification is a predictor of cardiovascular events such as, but not limited to, hypertension, stiffness, and even heart failure. Vascular smooth muscle cells (VSMCs), which line the arterial wall and function to maintain blood pressure, are hypothesized to undergo a phenotypic switch into bone-forming cells during calcification, mimicking the manner by which mesenchymal stem cells differentiate into osteoblast cells throughout osteogenesis. RunX2, a transcription factor necessary for osteoblast differentiation and a target gene of the Wnt signaling pathway, has also shown to be upregulated when calcification is present, implicating that the Wnt cascade may be a key player in the transdifferentiation of VSMCs. It is important to note that the phenotypic switch of VSMCs from a healthy, contractile state to a proliferative, synthetic state is necessary in response to the vascular injury surrounding calcification. The lingering question, however, is if VSMCs acquire this synthetic phenotype through the Wnt pathway, how and why does this signaling occur? This review seeks to highlight the potential role of the canonical Wnt signaling pathway within vascular calcification based on several studies and further discuss the Wnt ligands that specifically aid in VSMC transdifferentiation.

scholarly journals Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis

2020 ◽  
Author(s):  
Karlijn van Loon ◽  
Elisabeth J. M. Huijbers ◽  
Arjan W. Griffioen
Keyword(s):  
Wnt Signaling ◽  
Tumor Angiogenesis ◽  
Wnt Signaling Pathway ◽  
Tumor Vasculature ◽  
Great Promise ◽  
Cancer Therapies ◽  
Rich Domain ◽  
Metastatic Setting ◽  
Angiogenic Effect

Abstract Secreted frizzled-related proteins (SFRP) are glycoproteins containing a so-called frizzled-like cysteine-rich domain. This domain enables them to bind to Wnt ligands or frizzled (FzD) receptors, making potent regulators of Wnt signaling. As Wnt signaling is often altered in cancer, it is not surprising that Wnt regulators such as SFRP proteins are often differentially expressed in the tumor microenvironment, both in a metastatic and non-metastatic setting. Indeed, SFRP2 is shown to be specifically upregulated in the tumor vasculature of several types of cancer. Several studies investigated the functional role of SFRP2 in the tumor vasculature, showing that SFRP2 binds to FzD receptors on the surface of tumor endothelial cells. This activates downstream Wnt signaling and which is, thereby, stimulating angiogenesis. Interestingly, not the well-known canonical Wnt signaling pathway, but the noncanonical Wnt/Ca2+ pathway seems to be a key player in this event. In tumor models, the pro-angiogenic effect of SFRP2 could be counteracted by antibodies targeting SFRP2, without the occurrence of toxicity. Since tumor angiogenesis is an important process in tumorigenesis and metastasis formation, specific tumor endothelial markers such as SFRP2 show great promise as targets for anti-cancer therapies. This review discusses the role of SFRP2 in noncanonical Wnt signaling and tumor angiogenesis, and highlights its potential as anti-angiogenic therapeutic target in cancer.

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