Article
Biochemistry & Molecular Biology
Lauren L. Daniele, John Y. S. Han, Ivy S. Samuels, Ravikiran Komirisetty, Nikhil Mehta, Jessica L. McCord, Minzhong Yu, Yekai Wang, Kathleen Boesze-Battaglia, Brent A. Bell, Jianhai Du, Neal S. Peachey, Nancy J. Philp
Summary: Glucose supply is crucial for the normal functioning and survival of retinal cells. This study demonstrates the essential role of glucose in maintaining and sustaining rod photoreceptor outer segments (OS), with minimal impact on cone photoreceptor cells.
Article
Biology
Matthias Poege, Julia Mahamid, Sanae S. Imanishi, Juergen M. Plitzko, Krzysztof Palczewski, Wolfgang Baumeister
Summary: Studies have identified two molecular connectors/spacers in the membrane structure of rod outer segment (ROS) that likely contribute to the precise stacking of ROS disks. Additionally, a continuous supramolecular assembly composed of peripherin-2 (PRPH2) and rod outer segment membrane protein 1 (ROM1) oligomers enforces the extreme radius of curvature at the disk rims. Together, these molecular assemblies constitute the structural basis of the highly specialized ROS functional architecture.
Article
Medicine, Research & Experimental
Byunghwa Noh, John Hoon Rim, Ramu Gopalappa, Haiyue Lin, Kyu Min Kim, Min Jin Kang, Heon Yung Gee, Jae Young Choi, Hyongbum Henry Kim, Jinsei Jung
Summary: In vivo gene editing targeting outer hair cells using a dual adeno-associated virus package significantly improved auditory thresholds and a new live-cell imaging technique demonstrated the enhanced activity of KCNQ4 channels after disruption of mutant allele. These findings support the development of targeted therapies for DFNA2 and the potential use of CRISPR-based gene therapy to rectify defects in outer hair cells.
Article
Biochemistry & Molecular Biology
Alex J. McCann, Jieqiong Lou, Mehdi Moustaqil, Matthew S. Graus, Ailisa Blum, Frank Fontaine, Hui Liu, Winnie Luu, Paulina Rudolffi-Soto, Peter Koopman, Emma Sierecki, Yann Gambin, Frederic A. Meunier, Zhe Liu, Elizabeth Hinde, Mathias Francois
Summary: The study reveals that the mutant SOX18(RaOp) disrupts the system through molecular interferences, impairing the functions of wild-type SOX18 protein, and amplifying the dominant-negative effect by poisoning the interactome of its wild-type counterpart.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Neurosciences
Jillian N. Pearring, Jorge Martinez-Marquez, Jason R. Willer, Eric C. Lieu, Raquel Y. Salinas, Vadim Y. Arshavsky
Summary: The study found that the targeted delivery of the rod cyclic nucleotide-gated (CNG) channel to the outer segment uses the conventional secretory pathway and requires preassembly of its constituent alpha 1 and beta 1 subunits. The N-terminal glutamic acid-rich protein domain of CNG beta 1 encodes specific information targeting the channel to rod outer segments and connects the channel to photoreceptor disk rims through an interaction with peripherin-2. These findings reveal fine functional specializations within the CNG channel's structural domains and suggest that its sequestration to the outer segment plasma membrane requires an interaction with peripherin-2.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Moke Liu, Luna Liu, Honglin Guo, Xiude Fan, Tianbao Liu, Chao Xu, Zhao He, Yongfeng Song, Ling Gao, Shanshan Shao, Jiajun Zhao, Peng Lu
Summary: In this study, a mouse model carrying the HNF1a P291fsinsC mutation was established, and it was found that this mutation led to liver steatosis. Further analysis revealed changes in innate immune response and lipid metabolism pathways. The study also showed that HNF1a inhibited the expression of CFD in hepatocytes, and that CFD regulated hepatocyte lipid deposition.
Review
Biochemistry & Molecular Biology
Sahil Gulati, Krzysztof Palczewski
Summary: Visual phototransduction is a well-studied GPCR signaling pathway that plays a vital role in vision. Recent discoveries, through cryo-electron tomography and protein structural knowledge, have advanced our understanding of the morphology of rod outer segments (ROS) and the pathogenesis of retinal diseases. The reconstruction of the rod phototransduction system provides insights into the involvement of phosphodiesterase 6 (PDE6) and guanylate cyclases (GCs) in maintaining the spacing between ROS discs, shedding light on the generation of intrinsic optical signals in the retina.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xiaowen Shi, Hua Yang, Chen Chen, Jie Hou, Katherine M. Hanson, Patrice S. Albert, Tieming Ji, Jianlin Cheng, James A. Birchler
Summary: Genomic imbalance caused by aneuploidy has a more detrimental effect than that caused by ploidy changes, with varying effects on gene expression such as gene dosage effects, dosage compensation, and inverse correlation. The study reveals that gene expression changes in aneuploids affect both the varied chromosome and the rest of the genome, with a wider modulation range compared to whole-ploidy series. Kinetic considerations of multicomponent molecular interactions predict increased and decreased effects in gene expression modulation under genomic imbalance. This provides new insights into the mechanistic aspects of gene regulation.
Article
Cell Biology
Lucie Crouzier, Camille Diez, Elodie M. Richard, Nicolas Cubedo, Clement Barbereau, Mireille Rossel, Thomas Delaunay, Tangui Maurice, Benjamin Delprat
Summary: Retinitis pigmentosa (RP) is a common inherited retinal degeneration disease with no current treatment available. The zebrafish pde6a(Q70X) mutant serves as an ideal model for studying the progression of RP and potential treatments.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Amr Ghaleb, Lucia Roa, Natalia Marchenko
Summary: The biological consequences of low-dose radiation (LDR) in breast cancer are unclear, while high-dose radiation (HDR) promotes DNA repair and cell cycle arrest. Mutant p53 promotes mammary tumorigenesis following LDR, but has negligible effects on tumors carrying the wild-type p53 allele.
Article
Biochemistry & Molecular Biology
Anne Rehkamp, Dirk Tanzler, Christian Tuting, Panagiotis L. Kastritis, Claudio Iacobucci, Christian H. Ihling, Marc Kipping, Karl-Wilhelm Koch, Andrea Sinz
Summary: The study conducted a 3D-structural analysis of ROS-GC1 from bovine retina using cross-linking/mass spectrometry and computational modeling, revealing its active full-length structure and proposing a novel intracellular domain organization. The data supports a dimeric architecture of native ROS-GC1 from bovine retina and the integrated approach serves as a blueprint for conducting 3D-structural studies of membrane proteins in their native environment.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Harry Scott, Wei Huang, Kiran Andra, Sireesha Mamillapalli, Srinivas Gonti, Alexander Day, Kaiming Zhang, Nurjahan Mehzabeen, Kevin P. Battaile, Anjali Raju, Scott Lovell, James G. Bann, Derek J. Taylor
Summary: This study reveals the structure and transition mechanism of the tripartite protein complex produced by anthrax bacteria, which contributes to the understanding of the molecular mechanism of anthrax infection.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Evolutionary Biology
Emily Kuehn, David S. Clausen, Ryan W. Null, Bria M. Metzger, Amy D. Willis, B. Duygu Ozpolat
Summary: Development of sexual characters and gamete generation in Platynereis dumerilii is closely linked to growth. The study revealed a developmental transition dependent on the growth state of juvenile worms, leading to substantially increased germline expansion. Manipulations of segment numbers and environmental conditions supported the segment number threshold requirement for germline development in P. dumerilii.
JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION
(2022)
Article
Multidisciplinary Sciences
Tomohito Ohshima, Zhang Jiajun, Takuki Fukamachi, Yuko Ohno, Hiroko Senoo, Yasuhiro Matsuo, Makoto Kawamukai
Summary: This study identified a dominant negative allele, sam3, of the rad24 gene in the fission yeast Schizosaccharomyces pombe. The sam3 mutation allows mating without starvation and is caused by a change in nucleotide and amino acid at position 959 and 185, respectively. The Rad24-E185K mutant protein interacts differently with various proteins, leading to the sam phenotype and UV non-sensitivity. In addition, glucose depletion induces haploid meiosis in rad24-E185K or Delta pka1 Delta rad24 double mutants.
Article
Biology
Isabella Panfoli, Daniela Calzia, Silvia Ravera, Paolo Bianchini, Alberto Diaspro
Summary: The article presents a protocol that maximizes the yield of photoreceptor outer segments (OS) by minimizing the loss of OS embedded in the retinal pigmented epithelium (RPE). The protocol shows a 300% improvement in total protein yield and preserves the physiological features of the retina.
Article
Cell Biology
Rachayata Dharmat, Aiden Eblimit, Michael A. Robichaux, Zhixian Zhang, Thanh-Minh T. Nguyens, Sung Yun Jung, Feng He, Antrix Jain, Yumei Li, Jun Qin, Paul Overbeek, Ronald Roepman, Graeme Mardon, Theodore G. Wensel, Rui Chen
JOURNAL OF CELL BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Bo Yu, Anuoluwapo Egbejimi, Rachayata Dharmat, Pei Xu, Zhenyang Zhao, Bo Long, Hongyu Miao, Rui Chen, Theodore G. Wensel, Jiyang Cai, Yan Chen
Article
Neurosciences
Melina A. Agosto, Ivan A. Anastassov, Theodore G. Wensel
VISUAL NEUROSCIENCE
(2018)
Article
Biochemistry & Molecular Biology
Bo Yu, Anuoluwapo Egbejimi, Rachayata Dharmat, Pei Xu, Zhenyang Zhao, Bo Long, Hongyu Miao, Rui Chen, Theodore G. Wensel, Jiyang Cai, Yan Chen
Article
Biochemistry & Molecular Biology
Timothy L. Dosey, Zhao Wang, Guizhen Fan, Zhixian Zhang, Irina I. Serysheva, Wah Chiu, Theodore G. Wensel
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Maria E. Terron-Diaz, Sara J. Wright, Melina A. Agosto, Olivier Lichtarge, Theodore G. Wensel
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Michael A. Robichaux, Valencia L. Potter, Zhixian Zhang, Feng He, Jun Liu, Michael F. Schmid, Theodore G. Wensel
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Review
Cell Biology
Theodore G. Wensel
Review
Physiology
Theodore G. Wensel, Valencia L. Potter, Abigail Moye, Zhixian Zhang, Michael A. Robichaux
Summary: The rod and cone photoreceptor cells of the vertebrate retina have specialized structures that enable them to carry out light detection over a broad range of illumination intensities. These structures support their daily function and phototransduction through specialized organization.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Article
Medicine, Research & Experimental
Valencia L. Potter, Abigail R. Moye, Michael A. Robichaux, Theodore G. Wensel
Summary: Mutations in the CEP290 gene cause retinal degeneration. Studies using microscopy revealed the precise localization and functional roles of CEP290, indicating its crucial role in the connecting cilia of photoreceptors.
Article
Biochemistry & Molecular Biology
Melina A. Agosto, Abiodun Adefola R. Adeosun, Nitin Kumar, Theodore G. Wensel
Summary: This study investigates the role of mGluR6 in synaptic localization and function in the retinal photoreceptor signal transduction pathway. It was found that multiple regions in the ligand-binding domain of mGluR6 are necessary for synaptic localization and ELFN1 binding. The study proposes a model in which trans-synaptic ELFN1 binding is required for mGluR6 postsynaptic localization, while the C-terminus plays a role in mGluR6 in ON-BCs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Eunna Huh, Jonathan Gallion, Melina A. Agosto, Sara J. Wright, Theodore G. Wensel, Olivier Lichtarge
Summary: The study suggests that somatic mutations across class A GPCRs are nonrandomly distributed, with impactful, recurrent mutations at selected positions of functional motifs. These mutations induce perturbation of G protein activation and/or beta-arrestin recruitment in multiple receptors, promoting tumor growth or survival. The findings open a window into cancer mechanisms and potential therapeutic approaches by revealing that multiple GPCRs can drive or enable cancer through mutations at cognate positions across GPCR paralogs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Michael A. Robichaux, Vy Nguyen, Fung Chan, Lavanya Kailasam, Feng He, John H. Wilson, Theodore G. Wensel
Summary: The P23H-Rho-RFP mouse model provides a useful tool for studying the pathology and treatment of P23H-Rho and adRP. Mutant rod cells undergo an adaptive process that prolongs survival despite unfolded protein accumulation in the endoplasmic reticulum.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biology
Ammaji Rajala, Feng He, Robert E. Anderson, Theodore G. Wensel, Raju V. S. Rajala
Article
Neurosciences
Melina A. Agosto, Ivan A. Anastassov, Michael A. Robichaux, Theodore G. Wensel