4.4 Article

Striatins as plaque molecules of zonulae adhaerentes in simple epithelia, of tessellate junctions in stratified epithelia, of cardiac composite junctions and of various size classes of lateral adherens junctions in cultures of epithelia- and carcinoma-derived cells

Journal

CELL AND TISSUE RESEARCH
Volume 359, Issue 3, Pages 779-797

Publisher

SPRINGER
DOI: 10.1007/s00441-014-2053-z

Keywords

Adherens junctions; Tessellate junctions; Composite junctions; Intercalated disks; Arrhythmogenic ventricular cardiomyopathy (AC); Dilated cardiomyopathy (DC)

Categories

Funding

  1. German-Israeli Foundation for Scientific Research and Development (GIF) [I-1098-43.11/2010]

Ask authors/readers for more resources

Proteins of the striatin family (striatins 1-4; sizes ranging from 90 to 110 kDa on SDS-polyacrylamide gel electrophoresis) are highly homologous in their amino acid sequences but can differ in their cell-type-specific gene expression patterns and biological functions. In various cell types, we have found one, two or three polypeptides of this evolutionarily old and nearly ubiquitous family of proteins known to serve as scaffold proteins for diverse protein complexes. Light and electron microscopic immunolocalization methods have revealed striatins in mammalian cell-cell adherens junctions (AJs). In simple epithelia, we have localized striatins as constitutive components of the plaques of the subapical zonulae adhaerentes of cells, including intestinal, glandular, ductal and urothelial cells and hepatocytes. Striatins colocalize with E-cadherin or E-N-cadherin heterodimers and with the plaque proteins alpha- and beta-catenin, p120 and p0071. In some epithelia and carcinomas and in cultured cells derived therefrom, striatins are also seen in lateral AJs. In stratified epithelia and in corresponding squamous cell carcinomas, striatins can be found in plaques of some forms of tessellate junctions. Moreover, striatins are major plaque proteins of composite junctions (CJs; areae compositae) in the intercalated disks connecting cardiomyocytes, colocalizing with other CJ molecules, including plectin and ankyrin-G. We discuss the multimodulator scaffold roles of striatins in the initiation and regulation of the formation of various complex particles and structures. We propose that striatins are included in the diagnostic candidate list of proteins that, in the CJs of human hearts, can occur in mutated forms in the pathogeneses of hereditary cardiomyopathies, as seen in some types of genetically determined heart damage in boxer dogs.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.4
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Letter Cardiac & Cardiovascular Systems

The Heidelberg cardio-oncology unit (COUNT)-a possible blueprint for improved care of cardio-oncological patients

L. H. Lehmann, F. Stein, D. Jaeger, N. Frey

CLINICAL RESEARCH IN CARDIOLOGY (2022)

Letter Clinical Neurology

COVID-19-related severe MS exacerbation with life-threatening Takotsubo cardiomyopathy in a previously stable patient and interference of MS therapy with long-term immunity against SARS-CoV-2

Brigitte Wildemann, Sven Jarius, Lorenz H. Lehmann, Florian Andre, Norbert Frey, Paul Schnitzler, Laura Jaeger, Christoph Gumbinger, Andrea Viehover

JOURNAL OF NEUROLOGY (2022)

Article Medicine, General & Internal

Marathon-Induced Cardiac Strain as Model for the Evaluation of Diagnostic microRNAs for Acute Myocardial Infarction

Omid Shirvani Samani, Johannes Scherr, Elham Kayvanpour, Jan Haas, David H. Lehmann, Weng-Tein Gi, Karen S. Frese, Rouven Nietsch, Tobias Fehlmann, Steffi Sandke, Tanja Weis, Andreas Keller, Hugo A. Katus, Martin Halle, Norbert Frey, Benjamin Meder, Farbod Sedaghat-Hamedani

Summary: This study investigates the specificity of serum microRNAs as biomarkers for myocardial infarction by examining their behavior during strenuous exercise. The results show that some microRNAs associated with myocardial infarction have similar kinetics during exercise, suggesting limited diagnostic specificity. However, combining certain microRNAs with cardiac troponin within a multi-marker strategy may enhance diagnostic accuracy.

JOURNAL OF CLINICAL MEDICINE (2022)

Article Cardiac & Cardiovascular Systems

Pak2 Regulation of Nrf2 Serves as a Novel Signaling Nexus Linking ER Stress Response and Oxidative Stress in the Heart

Pablo Binder, Binh Nguyen, Lucy Collins, Min Zi, Wei Liu, Foteini Christou, Xiaojing Luo, Susanne S. Hille, Norbert Frey, Elizabeth J. Cartwright, Jonathan Chernoff, Oliver J. Mueller, Kaomei Guan, Xin Wang

Summary: This study identifies a novel regulator of Nrf2, Pak2, and elucidates the potential therapeutic significance of Pak2-mediated regulation of Nrf2 homeostasis in alleviating ER stress and heart failure.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2022)

Article Biology

Impact of Percutaneous Mitral Valve Repair Using the MitraClipTM System on Ventricular Arrhythmias and ICD Therapies

Nicolas A. Geis, Anna Goebbel, Michael M. Kreusser, Tobias Taeger, Hugo A. Katus, Norbert Frey, Philipp Schlegel, Philip W. Raake

Summary: This study aimed to assess the impact of TEER using the MitraClip(TM) device on ventricular arrhythmias and ICD therapies. The results showed that TEER significantly reduced ventricular arrhythmias and the need for ICD therapies.

LIFE-BASEL (2022)

Article Pathology

Programmed death-ligand 1 expression in the immune compartment of colon carcinoma

Osman Yilmaz, Amaya Pankaj, Azfar Neyez, Steffen Rickelt, Martin Taylor, Evan R. Lang, Lieve Leijsen, Anne Dinaux, Stuti G. Shroff, Rory Crotty, M. Lisa Zhang, Sandra Cerda, Qing Zhao, Cristina Ferrone, David T. Ting, Deepa T. Patil, Omer Yilmaz, David Berger, Vikram Deshpande

Summary: The expression of PD-L1 in colon carcinoma is associated with prognosis. High expression of PD-L1 is correlated with favorable pathological features and strong correlation with immune cells.

MODERN PATHOLOGY (2022)

Article Biochemistry & Molecular Biology

Genotype Complements the Phenotype: Identification of the Pathogenicity of an LMNA Splice Variant by Nanopore Long-Read Sequencing in a Large DCM Family

Farbod Sedaghat-Hamedani, Sabine Rebs, Elham Kayvanpour, Chenchen Zhu, Ali Amr, Marion Mueller, Jan Haas, Jingyan Wu, Lars M. Steinmetz, Philipp Ehlermann, Katrin Streckfuss-Boemeke, Norbert Frey, Benjamin Meder

Summary: In this study, a combination of genetic testing, iPSC-CMs and nanopore long-read sequencing was used to identify the causal variant in a multi-generational pedigree of DCM. The study highlighted the importance of precise diagnostics in the clinical management and workup of cardiomyopathies.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Biochemistry & Molecular Biology

Blockade of Wnt Secretion Attenuates Myocardial Ischemia-Reperfusion Injury by Modulating the Inflammatory Response

Ingmar Soren Meyer, Xue Li, Carina Meyer, Oksana Voloshanenko, Susann Pohl, Michael Boutros, Hugo Albert Katus, Norbert Frey, Florian Leuschner

Summary: This study tested the therapeutic potential of the Wnt secretion inhibitor LGK-974 in a model of ischemia/reperfusion injury and found that LGK-974 can attenuate inflammatory response, improve heart function, and potentially be used for immunomodulatory approaches to improve cardiac remodeling after myocardial infarction.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Review Cardiac & Cardiovascular Systems

A practical approach to the guideline-directed pharmacological treatment of heart failure with reduced ejection fraction

Amr Abdin, Johann Bauersachs, Samira Soltani, Matthias Eden, Norbert Frey, Michael Boehm

Summary: Heart failure remains a global healthcare challenge despite significant developments in pharmacotherapies. There are concerns regarding low medication dosages and incomplete drug classes in real-world settings, and current guidelines lack detailed recommendations. A practical approach algorithm is proposed to assist physicians in treating HF patients.

ESC HEART FAILURE (2023)

Article Cell Biology

Defining an abnormal p53 immunohistochemical stain in Barrett's oesophagus-related dysplasia: a single-positive crypt is a sensitive and specific marker of dysplasia

Kristen J. Tomaszewski, Azfar Neyaz, Kenan Sauder, Steffen Rickelt, M. Lisa Zhang, Omer Yilmaz, Rory Crotty, Stuti Shroff, Robert Odze, Anthony Mattia, Deepa T. Patil, Vikram Deshpande

Summary: Aimsp53 is an independent risk stratification marker in Barrett's esophagus (BE), but there is no universally accepted definition for abnormal p53 staining. This study assessed p53 staining in two cohorts to define abnormal p53 staining in BE-related dysplasia and evaluate the sensitivity and specificity of this cut-point for diagnosing dysplasia. The results showed that a single strongly positive p53 gland is highly sensitive and specific for dysplasia.

HISTOPATHOLOGY (2023)

Article Pharmacology & Pharmacy

Verapamil inhibits Kir2.3 channels by binding to the pore and interfering with PIP2 binding

Panagiotis Xynogalos, Ann-Kathrin Rahm, Sebastian Fried, Safak Chasan, Daniel Scherer, Claudia Seyler, Hugo A. Katus, Norbert Frey, Edgar Zitron

Summary: This study analyzed the effect of the antiarrhythmic drug verapamil on the inwardly rectifying potassium current of cardiomyocytes. The results showed that verapamil inhibited the Kir2.1, Kir2.2, and Kir2.3 channels, with the inhibition of Kir2.3 being a previously unknown finding. Further experiments revealed that the inhibition of Kir2.3 by verapamil was dependent on specific binding sites and interference with PIP2 activation. This finding provides a potential target for the development of selective antiarrhythmic drugs targeting Kir2.3 channels.

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY (2023)

Article Oncology

Proteomic Profiling of Extracellular Matrix Components from Patient Metastases Identifies Consistently Elevated Proteins for Developing Nanobodies That Target Primary Tumors and Metastases

Noor Jailkhani, Karl R. Clauser, Howard H. Mak, Steffen Rickelt, Chenxi Tian, Charles A. Whittaker, Kenneth K. Tanabe, Stephen R. Purdy, Steven A. Carr, Richard O. Hynes

Summary: Metastases, which are difficult to detect and treat, are the leading cause of cancer-related deaths. There is a clinical need for therapies specifically targeting metastases. This study focuses on developing nanobodies against extracellular matrix (ECM) proteins expressed in human metastases as potential vehicles for targeted delivery of imaging and therapeutic agents. By using phage-display libraries and proteomics, the researchers identified a conserved set of ECM proteins that are abundantly expressed in metastases from TNBC and colorectal cancer. They successfully isolated nanobodies against one of these proteins, tenascin-C (TNC), and demonstrated their specificity in binding TNBC tumors and metastases. The study suggests that generic nanobodies against tumors and metastases have great potential as cancer-agnostic tools for delivering therapeutics to the tumor microenvironment.

CANCER RESEARCH (2023)

Article Cell Biology

Predicting recurrence in pancreatic neuroendocrine tumours: role of ARX and alternative lengthening of telomeres (ALT)

Azfar Neyaz, Rory Crotty, Steffen Rickelt, Amaya Pankaj, Marija Stojanova, Theodoros P. Michelakos, Yurie Sekigami, Filippos Kontos, Paige H. Parrack, Deepa T. Patil, Christopher M. Heaphy, Cristina R. Ferrone, Vikram Deshpande

Summary: Immunohistochemistry for ARX and ALT FISH status can predict the aggressive behavior of nonfunctional PanNETs. This information can help identify patients who may benefit from surgical intervention.

HISTOPATHOLOGY (2023)

Meeting Abstract Medicine, General & Internal

Alcohol Consumption as another Risk Factor of TakoTsubo Cardiomyopathy - A monocentric Study

Lara Kluemper, Matthias Lutz, Norbert Frey

INTERNIST (2022)

Article Cardiac & Cardiovascular Systems

Comments on the guidelines (2021) of the ESC on the diagnosis and treatment of acute and chronic heart failure

Stefan Frantz, Stefan Anker, Johann Bauersachs, Michael Boehm, Jana Boer, Sonia Busch, Norbert Frey, Christian A. Perings, Tanja K. Rudolph, Stephan von Haehling, P. Christian Schulze

Summary: Heart failure is a syndrome with high morbidity and mortality. The new ESC guidelines provide the current standard for diagnosing and treating acute and chronic heart failure. The most significant change is the altered first-line treatment for heart failure with reduced ejection fraction.

KARDIOLOGIE (2022)

No Data Available