Article
Developmental Biology
Lena P. Basta, Michael Hill-Oliva, Sarah Paramore, Rishabh Sharan, Audrey Goh, Abhishek Biswas, Marvin Cortez, Katherine A. Little, Eszter Posfai, Danelle Devenport
Summary: Researchers introduced three new mouse models for investigating the localization and dynamics of transmembrane PCP proteins; using the skin epidermis as a model, they found that cell polarity dynamically changes during cell rearrangements and divisions, but the overall tissue polarity is maintained; through super-resolution STED imaging, they successfully observed the complex localization of PCP proteins along cell junctions.
Article
Biochemistry & Molecular Biology
Hui Wang, Friedemann Zaiser, Priska Eckert, Johannes Ruf, Nicolas Kayser, Anna C. Veenstra, Merle Mueller, Rebecca Haas, Gerd Walz, Toma A. Yakulov
Summary: Nephronophthisis (NPH), an autosomal recessive ciliopathy, is caused by mutations in more than 20 different genes (NPHPs). These mutations affect protein complexes involved in cilium trafficking and developmental processes. In this study, the zebrafish mutant line invssa36157 was used to investigate the tissue-specific functions of zebrafish Nphp2. The results showed that the invssa36157 mutants exhibited mild ciliopathy phenotypes, increased glomerular and cloaca cyst formation, and enhanced susceptibility to the depletion of the nphp1/nphp2/nphp8 module. The simultaneous knockdown of zebrafish nphp1 and vangl2 led to pronounced cloaca malformations in the invssa36157 mutant embryos, highlighting the role of these genes in normal cloaca formation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Developmental Biology
Antoine Donati, Isabelle Anselme, Sylvie Schneider-Maunoury, Christine Vesque
Summary: The study found that in the monociliated epithelium of the embryonic zebrafish floor-plate, basal bodies achieve posterior localization through dynamic movements and contacts with Par3 patches. The enrichment of Par3 plays a key role in controlling basal body positioning, providing new insights into the regulation of basal body positioning downstream of the PCP pathway.
Article
Cell Biology
Maria Beatriz Duran Alonso, Victor Vendrell, Iris Lopez-Hernandez, Maria Teresa Alonso, Donna M. Martin, Fernando Giraldez, Laura Carramolino, Giovanna Giovinazzo, Enrique Vazquez, Miguel Torres, Thomas Schimmang
Summary: Meis2 gene plays a crucial role in controlling the development of the inner ear, particularly in the formation of the cochlea. The expression of Meis2 in tissues required for inner ear induction and the hindbrain is essential for otic vesicle formation. Inactivation of Meis2 in the inner ear results in an aberrant coiling of the cochlear duct, suggesting its importance in proper cochlear morphogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Miguel Ramirez Moreno, Katy Boswell, Helen L. Casbolt, Natalia A. Bulgakova
Summary: Intracellular trafficking, regulated by the AP-1 complex, plays a crucial role in epithelial morphogenesis and cell adhesion. Knockdown of AP-1 leads to tissue folding and cell death, potentially acting as a tumor suppressor. Furthermore, E-cadherin hyperinternalization and increased expression contribute to cell-cell adhesion maintenance.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Biology
Shihai Jia, Evan M. Ratzan, Ellison J. Goodrich, Raisa Abrar, Luke Heiland, Basile Tarchini, Michael R. Deans
Summary: The vestibular maculae in the inner ear play a crucial role in detecting acceleration and coordinating balance. The transcription factor EMX2 is responsible for establishing the planar polarized organization in hair cells, and we have discovered that it negatively regulates the serine threonine kinase STK32A. STK32A is involved in aligning the polarity of hair cell bundles and reinforcing the formation of LPR.
Article
Biology
Kayla Davis, Himanish Basu, Ismael Izquierdo-Villalba, Ethan Shurberg, Thomas L. Schwarz
Summary: Mitochondrial transport relies on the interaction between Miro1 and other components of the motor-adaptor complex, and the N-GTPase domain of Miro1 plays a critical role in regulating this interaction and mitochondrial motility.
LIFE SCIENCE ALLIANCE
(2022)
Review
Anatomy & Morphology
Andiara E. E. Freitas, Lilach Gorodetski, Wei Ling Lim, Yimin Zou
Summary: This review summarizes the key evidence that PCP proteins may be responsible for the formation and stability of the majority of glutamatergic synapses, and how disruption of PCP protein function can lead to neurodegenerative, neurodevelopmental, and neuropsychiatric disorders. The PCP proteins may be the missing pieces of a long-standing puzzle and filling this knowledge gap may provide the basis for understanding many unsolved questions in synapse biology.
DEVELOPMENTAL DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Lea Reuter, Tanja Schmidt, Prabha Manishankar, Christian Throm, Jutta Keicher, Andrea Bock, Irina Droste-Borel, Claudia Oecking
Summary: NPH3 plays a crucial role in auxin-dependent plant phototropism, with blue light triggering its dissociation from the plasma membrane through phosphorylation and interaction with 14-3-3 proteins. In darkness, NPH3 binds polyacidic phospholipids for membrane association. The dynamic change in NPH3 localization mediated by 14-3-3 is essential for auxin-dependent phototropism.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Courtney A. Dreyer, Kacey VanderVorst, Dean Natwick, George Bell, Prachi Sood, Maria Hernandez, James M. Angelastro, Sean R. Collins, Kermit L. Carraway III
Summary: In this study, we found that the non-canonical Wnt planar cell polarity (Wnt/PCP) signaling pathway components Vangl1 and Fzd7 promote the malignancy of glioblastoma multiforme (GBM) by enhancing cellular proliferation, migration, and invasiveness. They also activate Rho GTPases to regulate cytoskeletal rearrangements and actin dynamics in migrating GBM cells. We discovered a novel Vangl1/Fzd7 complex at the leading edge of migratory GBM cells, which is critical for recruiting downstream effectors to promote tumor progression. Depletion of FZD7 resulted in suppressed tumor growth, delayed latency, and improved overall survival in a mouse xenograft model, suggesting that targeting the Wnt/PCP pathway could be a potential therapeutic strategy for GBM patients.
Article
Plant Sciences
Mei Xu, Xu Yan, Yutong Wang, Chan Liu, Qian Yang, Dan Tian, Sebastian Y. Bednarek, Jianwei Pan, Chao Wang
Summary: The study reveals that AP-1 plays a crucial role in pollen wall development by regulating protein transport in tapetal cells and microspores.
Article
Cell Biology
Rafael Mattera, Raffaella De Pace, Juan S. Bonifacino
Summary: Adaptor protein 4 (AP-4) is a complex that binds with AAGAB to promote its assembly and plays a role in the development of the central nervous system.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Genetics & Heredity
Michael Ebeid, Ippei Kishimoto, Pooja Roy, Mohd Ali Abbas Zaidi, Alan G. Cheng, Sung-Ho Huh
Summary: This study elucidates the role of beta-Catenin in establishing the identity of inner pillar cells (IPCs) in the mammalian cochlea. The transcriptional function of beta-Catenin is crucial for maintaining IPCs and preventing the formation of extranumerary outer pillar cells (OPCs). Overexpression of beta-Catenin promotes IPC proliferation without generating ectopic IPCs. Supporting cells lacking beta-Catenin transcriptional function show a loss of IPC signatures and gain of OPC signatures. Additionally, targeted deletion of beta-Catenin in IPCs leads to the loss of IPC identity. These findings contribute to future strategies for hair cell regeneration based on IPCs.
Article
Plant Sciences
Peng Wang, Wei Siao, Xiuyang Zhao, Deepanksha Arora, Ren Wang, Dominique Eeckhout, Jelle Van Leene, Rahul Kumar, Anaxi Houbaert, Nancy De Winne, Evelien Mylle, Michael Vandorpe, Ruud A. Korver, Christa Testerink, Kris Gevaert, Steffen Vanneste, Geert De Jaeger, Daniel Van Damme, Eugenia Russinova
Summary: Adaptor protein (AP) complexes play a crucial role in vesicle transport regulation. In plants, the AP complexes are involved in sorting cargoes and regulating endocytosis and post-Golgi trafficking routes. A comprehensive interactome analysis identified several hub proteins, including a previously unknown adaptin binding-like protein called P34, which interacts with AP complexes and controls their stability. This study provides important insights into the regulation of endomembrane trafficking in plant cells.
Article
Cell Biology
Matthew J. E. Logue, Rachel E. Farquhar, Yoakim Eckhoff-Bjorngard, Tanya T. Cheung, Daniel C. Devor, Fiona J. McDonald, Kirk L. Hamilton
Summary: Control of ion and water movement across epithelia is crucial for maintaining homeostasis. The exocyst complex plays a crucial role in regulating the connection between KCa3.1 ion channels and the basolateral membrane in epithelial cells.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Behavioral Sciences
Victor Faundez, Meghan Wynne, Amanda Crocker, Daniel Tarquinio
FRONTIERS IN INTEGRATIVE NEUROSCIENCE
(2019)
Review
Cell Biology
Cortnie Hartwig, Stephanie A. Zlatic, Melissa Wallin, Alysia Vrailas-Mortimer, Christoph J. Fahrni, Victor Faundez
CURRENT OPINION IN CELL BIOLOGY
(2019)
Article
Neurosciences
Frank Y. Lee, Jennifer Larimore, Victor Faundez, Esteban C. Dell'Angelica, Cristina A. Ghiani
Summary: The absence of BLOC-1 during brain development affects male mice more than females, particularly in the hippocampus. While most abnormalities in juvenile animals seem to have been resolved, potential permanent defects may result in faulty neuronal circuits and contribute to cognitive and behavioral phenotypes in adult BLOC-1-deficient mice.
JOURNAL OF NEUROSCIENCE RESEARCH
(2021)
Editorial Material
Biochemistry & Molecular Biology
Gopal P. Sarma, Allan Levey, Victor Faundez
Article
Neurosciences
Pernille Bulow, Stephanie A. Zlatic, Peter A. Wenner, Gary J. Bassell, Victor Faundez
Summary: This study found an increased number of mitochondrial annotated proteins in the proteome of cortical neurons sensitive to both activity deprivation and Fmr1(-/y) genotype, suggesting a novel role of FMRP in attenuating mitochondrial proteome modifications induced by activity deprivation.
Article
Cell Biology
Jessica N. Peoples, Nasab Ghazal, Duc M. Duong, Katherine R. Hardin, Janet R. Manning, Nicholas T. Seyfried, Victor Faundez, Jennifer Q. Kwong
Summary: Mitochondria can trigger various signaling pathways under stress conditions, with mitochondrial energy dysfunction leading to a pattern of acylome remodeling. This remodeling specifically impacts mitochondrial proteins, with acetylation and malonylation modifying the interactome and enzyme activity within mitochondria. Additionally, a novel cross talk between acetylation and malonylation was discovered, indicating a mechanism by which disruption to energy production can impact global mitochondrial function.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Editorial Material
Cell Biology
Kaela S. Singleton, Victor Faundez
Summary: In this study, Bowman et al. illustrate a novel mechanism where AP-3 and BLOC-1 complexes, together with syntaxin 13, act as a fail-safe system to recognize sorting signals in VAMP7, ensuring its loading into nascent carriers. This observation represents one of the first instances of distributed robustness in membrane traffic mechanisms.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Neurosciences
Meghan E. Wynne, Alicia R. Lane, Kaela S. Singleton, Stephanie A. Zlatic, Avanti Gokhale, Erica Werner, Duc Duong, Jennifer Q. Kwong, Amanda J. Crocker, Victor Faundez
Summary: The mitochondrial composition varies among brain regions and neuronal cell types, as shown in a study on mice. Single-cell mitochondrial transcriptomes can distinguish different types of neurons, indicating that mitochondrial heterogeneity may influence specific mechanisms in health and disease.
Article
Multidisciplinary Sciences
Thomas S. Wingo, Yue Liu, Ekaterina S. Gerasimov, Selina M. Vattathil, Meghan E. Wynne, Jiaqi Liu, Adriana Lori, Victor Faundez, David A. Bennett, Nicholas T. Seyfried, Allan Levey, Aliza P. Wingo
Summary: The study finds evidence for shared genetic and molecular pathophysiology between several common psychiatric and neurodegenerative diseases, which has important implications for early treatment and therapeutic development.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Pernille Bulow, Anupam Patgiri, Victor Faundez
Summary: The human brain consumes a significantly larger amount of energy than the sun by unit of mass and time. Defects in the machinery for cellular energy production, particularly in mitochondrial protein synthesis, may be a causative mechanism for neurodevelopmental and behavioral disorders.
Article
Cell Biology
E. Werner, A. Gokhale, M. Ackert, C. Xu, Z. Wen, A. M. Roberts, B. R. Roberts, A. Vrailas-Mortimer, A. Crocker, V Faundez
Summary: By studying genetic cellular models, we found that manganese exposure compromises the function and composition of mitochondrial RNA granules, leading to disruption of mitochondrial transcript processing and respiratory chain function. Interestingly, impaired RNA granule function acts as a protective mechanism against acute manganese toxicity.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Multidisciplinary Sciences
Stephanie A. Zlatic, Duc Duong, Kamal K. E. Gadalla, Brenda Murage, Lingyan Ping, Ruth Shah, James J. Fink, Omar Khwaja, Lindsay C. Swanson, Mustafa Sahin, Sruti Rayaprolu, Prateek Kumar, Srikant Rangaraju, Adrian Bird, Daniel Tarquinio, Randall Carpenter, Stuart Cobb, Victor Faundez
Summary: This study investigates the proteome of Rett cerebrospinal fluid (CSF) and identifies proteins associated with HDL lipoproteins, complement, mitochondria, citrate/pyruvate metabolism, synapse compartments, and the neurosecretory protein VGF. The differentially expressed CSF proteins can distinguish Rett syndrome from a related neurodevelopmental disorder. These findings provide insights into potential mechanisms and biomarkers of Rett syndrome.
Article
Biology
Meghan E. Wynne, Oluwaseun Ogunbona, Alicia R. Lane, Avanti Gokhale, Stephanie A. Zlatic, Chongchong Xu, Zhexing Wen, Duc M. Duong, Sruti Rayaprolu, Anna Ivanova, Eric A. Ortlund, Eric B. Dammer, Nicholas T. Seyfried, Blaine R. Roberts, Amanda Crocker, Vinit Shanbhag, Michael Petris, Nanami Senoo, Selvaraju Kandasamy, Steven Michael Claypool, Antoni Barrientos, Aliza Wingo, Thomas S. Wingo, Srikant Rangaraju, Allan I. Levey, Erica Werner, Victor Faundez
Summary: This study demonstrates that mitochondria play a role in regulating the secretome, specifically the upregulation of APOE and other secretome components. Disruption of the electron transport chain, either genetically or pharmacologically, leads to the upregulation of APOE transcript, protein, and secretion. These findings suggest that mitochondria act as upstream regulators of APOE-dependent processes and may play a role in neurodegeneration and Alzheimer's disease.