Article
Cell Biology
Anuttoma Ray, Parmender P. Mehta
Summary: Cx32 was found to be palmitoylated at cysteine 217 (C217) in cell line derived from prostate tumors, but mutating C217 to alanine had no effect on its function. Mutation of cysteine 280 and 283, only in combination, blocked the trafficking of Cx32 from the trans-Golgi network to the cell surface, leading to reduced stability.
CELLULAR SIGNALLING
(2021)
Review
Cell Biology
Stefan Dhein, Aida Salameh
Summary: The heart relies on gap junction channels to maintain cell-cell coupling for efficient and rapid electrical conduction. Connexin expression and gap junction localization play crucial roles in modulating cardiac electrical properties, ultimately affecting cardiac stability and function.
Review
Cell Biology
Peter Bedner, Christian Steinhaeuser
Summary: The gap-junction-coupled astroglial network is essential for regulating neuronal activity and synchronization, but its role in the pathogenesis of neuronal diseases is still unclear. This paper summarizes the current knowledge about the impact of impaired glial coupling in epilepsy and discusses the potential of astrocytes as therapeutic targets. It focuses on temporal lobe epilepsy (TLE), the most common form of epilepsy in adults, characterized by high therapy resistance. Studies suggest a complete loss of astrocytic coupling in TLE, preceding dysfunctional changes in neurons, indicating that astrocyte uncoupling may be a causal event in epilepsy initiation. However, further research is needed to fully understand the role of gap junction channels in epilepsy and develop effective therapeutic strategies targeting astrocytes.
Review
Biochemistry & Molecular Biology
Jennifer C. Jones, Thomas M. Bodenstine
Summary: Connexins are important membrane channel proteins that regulate both intercellular communication and cellular metabolism in cancer cells. They have diverse roles in cancer biology, being able to promote or suppress cancer cell function. The relationship between glucose metabolism and connexin function in cancer cells is complex and requires further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andres Tittarelli
Summary: Connexin-mediated intercellular communication mechanisms play important roles in immune system activities, especially in infections, wounds, cancer, and other inflammatory conditions. Modulating connexin expression and channel activities may be a promising approach for designing therapeutic tools.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Neurosciences
Xinyu Wang, Chuan Jiang, Chunli Lu, Longbing Ma, Yuxin Feng, Shengyu Cui, Qian Li, Kang Li, Xiang Wang, Fengzeng Jian
Summary: In this study, changes in the number and morphology of ependymal cilia in a syringomyelia rat model were investigated. The results showed a decline in cilia during the early stage of the disease, leading to disrupted intercellular communication. In the later stage, cilia were further reduced due to shear stress exposure, causing a potential mechanism of ependymal cilia decline in syringomyelia development.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yuefang Zhou, Thomas M. Bennett, Thomas W. White, Alan Shiels
Summary: CHMP4B is a core sub-unit of the ESCRT-III machinery involved in remodeling and scission processes of biological membranes. It has been found to associate with connexin 46 (Cx46) and connexin 50 (Cx50), and its membrane localization is dependent on Cx50 in lens fiber cells.
Review
Cell Biology
Andrew M. Boal, Michael L. Risner, Melissa L. Cooper, Lauren K. Wareham, David J. Calkins
Summary: Astrocytes play a crucial role in responding to neurodegenerative stress and are interconnected through gap junctions, primarily composed of connexin-43 (Cx43), forming a broader network. This network contributes to various important processes and is likely to influence the progression of neurodegenerative diseases. Targeting these networks may be critical in the treatment of glaucomatous neurodegeneration and other optic neuropathies.
Article
Cell Biology
Sergiu A. A. Lucaciu, Rhett Figliuzzi, Ruth Neumann, Samina Nazarali, Luigi Del Sordo, Stephanie E. E. Leighton, Alexandra Hauser, Qing Shao, Danielle Johnston, Donglin Bai, Dale W. W. Laird
Summary: Epidermal keratinocytes contain multiple connexins that regulate epidermal homeostasis. Mutations in the GJB4 gene encoding Cx30.3 are associated with a rare skin disorder called EKVP. In this study, researchers characterized three Cx30.3 mutants and found that they were non-functional and had trafficking impairments. Co-expression of wild type Cx30.3 enhanced the assembly of mutants into gap junctions, suggesting potential therapeutic value in rescuing epidermal defects.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Weiqi Zeng, Zhizhao Deng, Yingxin Gao, Guoliang Sun, Xianlong Li, Dongdong Yuan
Summary: Long-term exposure to Ang II significantly enhances the expression and function of Cx43-GJs in HUASMCs, leading to the accumulation of intracellular Ca2+ and the activation of downstream signaling pathways. However, propofol inhibits the function of Cx43-GJs in Ang II-pretreated HUASMCs, resulting in the inhibition of intracellular Ca2+ and its downstream signaling pathways and ultimately excessive relaxation of HUASMCs. This explains why patients with chronic hypertension experience more severe blood pressure fluctuations after propofol induction.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Santipongse Chatchavalvanich, Robert A. Boomsma, Jack M. Tietema, David L. Geenen
Summary: Early coupling between bone marrow-derived mesenchymal stem cells (BM-MSC) and ischemic cardiomyocytes through gap junctions (GJ) may play a crucial role in cell survival and retention in the acute phase of myocardial ischemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Avigail Ehrlich, Filippo Molica, Aurelie Hautefort, Brenda R. Kwak
Summary: This review provides an overview of the expression and function of connexins and pannexins in the lymphatic vasculature, focusing on their roles in healthy lymphatic system functions and pathological conditions. The discussion highlights their impact on intercellular communication, immune cell trafficking, and nutrient absorption, as well as their implications in lymphatic disorders and cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Rasheed A. Bailey, Derek L. Beahm, I. Martha Skerrett
Summary: Glycine is an amino acid with unique properties due to its single hydrogen atom side chain. Conserved glycines in proteins often indicate domains involving tight turns or bends. Substitutions at position 12 of certain connexins lead to alterations in function and have been linked to hereditary skin disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Olivia E. Crouthamel, Leping Li, Michael T. Dilluvio, Thomas W. White
Summary: Mutations in the GJA1 gene encoding connexin43 (Cx43) have been linked to various rare genetic disorders, including those affecting the skin. This study investigated the functional consequences of a specific Cx43 mutation (Cx43-G38E) associated with a novel human phenotype. The research showed that the mutation increased the activity of hemichannels, suggesting a potential role in skin and skeletal disorders caused by Cx43 mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Max Zachrisson Totland, Yasufumi Omori, Vigdis Sorensen, Kushtrim Kryeziu, Trond Aasen, Andreas Brech, Edward Leithe
Summary: Gap junctions are clusters of channels in the plasma membrane that enable the diffusion of ions and small molecules between adjacent cells, playing a fundamental role in coordinating tissue functions. The loss of intercellular communication mediated by gap junctions, often observed in cancer pathogenesis, can impact tumor growth and response to treatment. Connexins, integral membrane proteins, not only facilitate cell-cell communication but also modulate signal transduction pathways, cell processes, and the dynamic regulation of gap junction levels. Dysregulation of connexin trafficking in the endocytic system contributes to the loss of gap junctions during carcinogenesis, with potential therapeutic implications in cancer treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Jaya Aseervatham, Xiaofan Li, Cheryl K. Mitchell, Ya-Ping Lin, Ruth Heidelberger, John O'Brien
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Genetics & Heredity
Kadir C. Akdemir, Victoria T. Le, Justin M. Kim, Sarah Killcoyne, Devin A. King, Ya-Ping Lin, Yanyan Tian, Akira Inoue, Samirkumar B. Amin, Frederick S. Robinson, Manjunath Nimmakayalu, Rafael E. Herrera, Erica J. Lynn, Kin Chan, Sahil Seth, Leszek J. Klimczak, Moritz Gerstung, Dmitry A. Gordenin, John O'Brien, Lei Li, Yonathan Lissanu Deribe, Roel G. Verhaak, Peter J. Campbell, Rebecca Fitzgerald, Ashby J. Morrison, Jesse R. Dixon, P. Andrew Futreal
Article
Cell Biology
Abirami Santhanam, Eyad Shihabeddin, Joshua A. Atkinson, Duc Nguyen, Ya-Ping Lin, John O'Brien
Article
Neurosciences
Alejandro Vila, Eyad Shihabeddin, Zhijing Zhang, Abirami Santhanam, Christophe P. Ribelayga, John O'Brien
Summary: Synaptic signaling complexes are formed by scaffold proteins that interact with various other proteins and ion channels, with Chapsyn110 and SAP102 playing important roles in the synaptic connections between horizontal cells and photoreceptors in the mouse retina. The presence of inward rectifier potassium channel Kir2.1 with Chapsyn110 suggests its potential involvement in hyperpolarization-activated current in photoreceptor synapses. Daily rhythms of polyamine content in photoreceptor terminals may modulate the behavior of ion channels within the synapses.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
E. Anne Martin, Jennifer Carlisle Michel, Jane S. Kissinger, Fabio A. Echeverry, Ya-Ping Lin, John O'Brien, Alberto E. Pereda, Adam C. Miller
Summary: The subcellular positioning and molecular compositions of synapses are crucial for neural circuits. This study investigates the localization of the autism- and epilepsy-associated gene Neurobeachin, the Connexins, and the electrical synapse scaffold ZO1. It is found that Neurobeachin localizes to the electrical synapse independently, and its presence is necessary for the localization of ZO1 and Connexins. This research provides new insights into the molecular complexity and mechanisms of electrical synapse formation.
Article
Neurosciences
Ashley A. Farre, Chi Sun, Margaret R. Starostik, Samuel S. Hunter, Milton A. English, Audrey Duncan, Abirami Santhanam, Eyad Shihabeddin, John O'Brien, Anand Swaroop, Deborah L. Stenkamp
Summary: This study aimed to investigate the transcriptional heterogeneity and regulation of differentially expressed tandemly-replicated opsins using zebrafish as a model. The results showed additional transcriptional differences beyond opsin expression between LWS1 and LWS2 cones, which are likely controlled by multiple signals.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Yuan-Hao Lee, W. Wade Kothmann, Ya-Ping Lin, Alice Z. Chuang, Jeffrey S. Diamond, John O'Brien
Summary: Synaptic plasticity is a fundamental feature of the central nervous system, controlling the magnitude of signal transmission. Many electrical synapses exhibit plasticity that modulates neuronal coupling, signal fidelity, and circuit configuration. This plasticity is calcium-dependent and associated with neuronal activity.
Article
Biochemistry & Molecular Biology
Abirami Santhanam, Eyad Shihabeddin, Haichao Wei, Jiaqian Wu, John O'Brien
Summary: This study analyzed single-cell transcriptome data from zebrafish retina to understand the transcriptional changes in different cell types in a model of retinitis pigmentosa. The study found that oxidative stress is widespread throughout the retina, affecting various cell types and leading to an increase in oxidative metabolism and glycolysis. There was also evidence of synaptic remodeling and enhanced glutamatergic transmission in the inner retina. Additionally, changes in circadian rhythm regulation and the transcriptomic signatures of retinal progenitor cells and newly formed rods were identified.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Stephan Tetenborg, Helen Y. Wang, Lena Nemitz, Anne Depping, Alexsandra B. Espejo, Jaya Aseervatham, Mark T. Bedford, Ulrike Janssen-Bienhold, John O'Brien, Karin Dedek
SCIENTIFIC REPORTS
(2020)
Article
Neurosciences
Keith B. Moore, Cheryl K. Mitchell, Ya-Ping Lin, Yuan-Hao Lee, Eyad Shihabeddin, John O'Brien
Meeting Abstract
Ophthalmology
Yuan-Hao Lee, Alice Chuang, John O'Brien
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)
Meeting Abstract
Ophthalmology
Ya-Ping Lin, Ye Long, Cheryl Mitchell, Zhijing Zhang, Steven W. Wang, Stephen L. Mills, Chai-An Mao, Christophe Ribelayga, John O'Brien
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)
Meeting Abstract
Ophthalmology
Jaya Aseervatham, Helen Wang, Alexsandra Espejo, Cheryl Mitchell, Mark Bedford, John O'Brien
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)
Meeting Abstract
Ophthalmology
Abirami Santhanam, Eyad Shihabeddin, Josh Atkinson, Duc Nguyen, John O'Brien
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)
Meeting Abstract
Ophthalmology
Eyad Shihabeddin, Haichao Wei, Abirami Santhanam, Jiaqian Wu, John O'Brien
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)