Article
Cell Biology
Nan-Peng Chen, Jonas Aretz, Reinhard Faessler
Summary: The CDK1-cyclin B1 complex phosphorylates kindlin to induce its degradation, leading to the disassembly of focal adhesions and cell rounding at mitotic entry.
NATURE CELL BIOLOGY
(2022)
Review
Cell Biology
Marta Ripamonti, Bernhard Wehrle-Haller, Ivan de Curtis
Summary: Focal adhesions are cell structures that anchor cells to the extracellular matrix and also play a role in mechanosignaling by integrating physical and chemical cues from the microenvironment. Paxillin, a protein involved in focal adhesion formation and scaffolding, appears to have a key role in integrating multiple signals and activating various molecular responses from the microenvironment. This minireview provides an overview of the molecular mechanisms underlying the mechanosensitivity and mechanosignaling capacity of core focal adhesion proteins, with a focus on the role of paxillin.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Liang Zhu, Edward F. Plow, Jun Qin
Summary: Focal adhesions (FAs) are integrin-containing protein complexes regulated by a network of hundreds of protein-protein interactions. Despite the lack of a detailed understanding on how FAs are organized and function, advances have been made on studying key integrin activators, talin and kindlin.
Review
Cell Biology
Wenting Bu, Zarina Levitskaya, Suet-Mien Tan, Yong-Gui Gao
Summary: Kindlins are important positive regulators of integrin activation, and recent studies on their atomic structures have greatly advanced our understanding of their molecular functions. Oligomerization of kindlins may play a role in regulating integrin binding and focal adhesion localization.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Minjeong Yeon, Irene Bertolini, Ekta Agarwal, Jagadish C. Ghosh, Hsin-Yao Tang, David W. Speicher, Frederick Keeney, Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Edward F. Plow, Lucia R. Languino, Emmanuel Skordalakes, M. Cecilia Caino, Dario C. Altieri
Summary: In this study, it is found that the altered ubiquitination ligase Parkin in Parkinson's disease forms a complex with the regulator of cell motility Kindlin-2 at mitochondria of tumor cells. Parkin ubiquitinates Kindlin-2 leading to its proteasomal degradation, which inhibits tumor cell interactions with the extracellular matrix, migration, and invasion. However, Parkin does not affect tumor cell proliferation, cell cycle transitions, or apoptosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Editorial Material
Hematology
Andreas Margraf, Alexander Zarbock
Summary: The authors elegantly demonstrate that kindlin-3 recruitment to the membrane precedes integrin high-affinity activation and is dependent on the pleckstrin homology (PH) domain within kindlin-3.
Article
Cell Biology
Julien Pernier, Marcelina Cardoso Dos Santos, Mariem Souissi, Adrien Joly, Hemalatha Narassimprakash, Olivier Rossier, Gregory Giannone, Emmanuele Helfer, Kheya Sengupta, Christophe Le Clainche
Summary: Focal adhesions are essential for cell adhesion, in which talin and kindlin play important roles. This study demonstrates that talin and kindlin can individually cluster integrins and work together to form larger integrin clusters. The findings provide insights into the mechanism of integrin clustering.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cell Biology
Sarah Klapproth, Karsten Richter, Clara Tuerk, Theresa Bock, Thomas Bromberger, Julian Dominik, Kathrin Huck, Kristian Pfaller, Michael W. Hess, Christoph A. Reichel, Marcus Krueger, Inaam A. Nakchbandi, Markus Moser
Summary: This study reveals the crucial role of kindlin-3 in osteoclasts by regulating integrin activity and promoting the formation of bone sealing zones. Low expression of kindlin-3 leads to impaired adhesion and signaling in osteoclasts, resulting in ineffective digestion of bone matrix by the sealing zones.
JOURNAL OF CELL SCIENCE
(2021)
Article
Genetics & Heredity
Hiroshi Qadota, Annie McPherson, Rachel Corbitt, Evan Kelton Dackowski, Yohei Matsunaga, Andres Oberhauser, Guy M. Benian
Summary: The binding of UNC-112 to PAT-4 is essential for the localization and function of PAT-4 in Integrin adhesion complexes.
G3-GENES GENOMES GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Md Saimon Mia, Yagna Jarajapu, Reena Rao, Sijo Mathew
Summary: This study revealed a novel mechanism of integrin beta 1 in tumor growth by modulating the expression of kindlin-2 and TGF-beta receptor 2 signaling. Loss of integrin beta 1 affects cell proliferation and adhesion in a 3D matrix, thus impacting tumor growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Lei Qin, Xuekun Fu, Jing Ma, Manxia Lin, Peijun Zhang, Yishu Wang, Qinnan Yan, Chu Tao, Wen Liu, Bin Tang, Di Chen, Xiaochun Bai, Huiling Cao, Guozhi Xiao
Summary: The study reveals that the absence of Kindlin-2 in osteocytes leads to osteopenia and mechanical property defects, affecting skeletal responses to mechanical stimulation in long bones. Experimental results demonstrate that Kindlin-2 maintains skeletal responses to mechanical stimulation by regulating Sclerostin expression.
COMMUNICATIONS BIOLOGY
(2021)
Article
Hematology
Lai Wen, Alex Marki, Payel Roy, Sara McArdle, Hao Sun, Zhichao Fan, Alexandre R. Gingras, Mark H. Ginsberg, Klaus Ley
Summary: The study demonstrated the essential role of kindlin-3 in neutrophil adhesion, with its PH domain playing a crucial role in recruitment to the plasma membrane.
Review
Cell Biology
Moses Musiime, Joan Chang, Uwe Hansen, Karl E. Kadler, Cedric Zeltz, Donald Gullberg
Summary: Increased awareness of the importance of extracellular matrix composition has led to a renewed interest in understanding how cells recognize and remodel the matrix. Fibronectin and fibrillar collagens are key proteins in the matrix, with integrins directly anchoring cells to collagen and supporting collagen fibrillogenesis.
Article
Hematology
Dorota Szpak, Chloe Turpin, Utku Goreke, Katarzyna Bialkowska, Kamila M. Bledzka, Dmitriy Verbovetskiy, Narla Mohandas, Umut A. Gurkan, Jun Qin, Edward F. Plow, Elzbieta Pluskota
Summary: Kindlin-3 (K3) is crucial for the activation of integrin adhesion receptors in hematopoietic cells. Deficiency of K3 in erythroid and myeloid cells leads to anemia and misshaped erythrocytes, respectively. K3 has a dual function in erythrocytes and erythroblastic islands, playing a critical role in erythropoiesis and maintaining the integrity of erythrocyte shape through F-actin binding.
Article
Hematology
Huong T. T. Nguyen, Zhen Xu, Xiaofeng Shi, Shuzhen Liu, Marie L. Schulte, Gilbert C. White, Yan-Qing Ma
Summary: The study identified a previously unrecognized paxillin binding site in the PH domain of kindlin-3, which plays an important role in supporting integrin alpha IIb beta 3 outside-in signaling in platelets. Disruption of paxillin binding inhibited platelet spreading on immobilized fibrinogen, while treatment with a specific membrane-permeable peptide derived from the PH domain of kindlin-3 reduced thrombus formation in mice. These findings highlight a novel antithrombotic target involving the interaction between paxillin and the PH domain of kindlin-3.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Biochemistry & Molecular Biology
Eike-Christian Wamhoff, Jonas Hanske, Lennart Schnirch, Jonas Aretz, Maurice Grube, Daniel Varon Silva, Christoph Rademacher
ACS CHEMICAL BIOLOGY
(2016)
Article
Chemistry, Multidisciplinary
Jonas Aretz, Paul Robin Wratil, Eike-Christian Wamhoff, Hoang Giang Nguyen, Werner Reutter, Christoph Rademacher
CANADIAN JOURNAL OF CHEMISTRY
(2016)
Article
Chemistry, Multidisciplinary
J. Aretz, Y. Kondoh, K. Honda, U. R. Anumala, M. Nazare, N. Watanabe, H. Osada, C. Rademacher
CHEMICAL COMMUNICATIONS
(2016)
Article
Biochemistry & Molecular Biology
Jonas Hanske, Jessica Schulze, Jonas Aretz, Ryan McBride, Bernhard Loll, Henrik Schmidt, Yuriy Knirel, Wolfgang Rabsch, Markus C. Wahl, James C. Paulson, Christoph Rademacher
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Fumi Ota, Tetsuya Hirayama, Yasuhiko Kizuka, Yoshiki Yamaguchi, Reiko Fujinawa, Masahiro Nagata, Hendra S. Ismanto, Bernd Lepenies, Jonas Aretz, Christoph Rademacher, Peter H. Seeberger, Takashi Angata, Shinobu Kitazume, Keiichi Yoshida, Tomoko Betsuyaku, Kozui Kida, Sho Yamasaki, Naoyuki Taniguchi
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2018)
Article
Biochemistry & Molecular Biology
Felix Broecker, Jonas Aretz, You Yang, Jonas Hanske, Xiaoqiang Guo, Anika Reinhardt, Annette Wahlbrink, Christoph Rademacher, Chakkumkal Anish, Peter H. Seeberger
ACS CHEMICAL BIOLOGY
(2014)
Article
Chemistry, Multidisciplinary
Daniela Ponader, Pauline Maffre, Jonas Aretz, Daniel Pussak, Nina M. Ninnemann, Stephan Schmidt, Peter H. Seeberger, Christoph Rademacher, G. Ulrich Nienhaus, Laura Hartmann
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2014)
Article
Biochemistry & Molecular Biology
Jessica Schulze, Hannes Baukmann, Robert Wawrzinek, Felix F. Fuchsberger, Edgar Specker, Jonas Aretz, Marc Nazare, Christoph Rademacher
ACS CHEMICAL BIOLOGY
(2018)
Article
Chemistry, Multidisciplinary
Jonas Aretz, Upendra R. Anumala, Felix F. Fuchsberger, Narges Molavi, Nandor Ziebart, Hengxi Zhang, Marc Nazare, Christoph Rademacher
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2018)
Article
Chemistry, Multidisciplinary
Jonas Aretz, Christoph Rademacher
FRONTIERS IN CHEMISTRY
(2019)
Article
Biology
Ralph T. Boettcher, Nico Strohmeyer, Jonas Aretz, Reinhard Faessler
Summary: This study found that widely used antibodies against β1-pT788/pT789 integrin could not specifically detect the phosphorylation signal of the integrin. Instead, these antibodies bind to bi-phosphorylated threonine residues in multiple proteins. Additionally, the study also found that a phospho-mimicking β1-TT788/789DD integrin impairs integrin function due to the inability of kindlin to bind to the phosphorylated or phospho-mimicking β1-tail.
LIFE SCIENCE ALLIANCE
(2022)
Article
Chemistry, Medicinal
Dimitrios Spiliotopoulos, Jian Zhu, Eike-Christian Wamhoff, Nicholas Deerain, Jean-Remy Marchand, Jonas Aretz, Christoph Rademacher, Amedeo Caflisch
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Multidisciplinary
Jonas Aretz, Hannes Baukmann, Elena Shanina, Jonas Hanske, Robert Wawrzinek, Viktor A. Zapol'skii, Peter H. Seeberger, Dieter E. Kaufmann, Christoph Rademacher
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2017)
Article
Physiology
Congxiao Gao, Reiko Fujinawa, Takayuki Yoshida, Manabu Ueno, Fumi Ota, Yasuhiko Kizuka, Tetsuya Hirayama, Hiroaki Korekane, Shinobu Kitazume, Toshitaka Maeno, Kazuaki Ohtsubo, Keiichi Yoshida, Yoshiki Yamaguchi, Bernd Lepenies, Jonas Aretz, Christoph Rademacher, Hiroki Kabata, Ahmed E. Hegab, Peter H. Seeberger, Tomoko Betsuyaku, Kozui Kida, Naoyuki Taniguchi
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2017)
