4.1 Review

BORG family proteins in physiology and human disease

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Article Biochemistry & Molecular Biology

Dissecting the Binding Interface of the Septin Polymerization Enhancer Borg BD3

Danielle K. S. V. Castro et al.

Summary: The molecular basis for septin filament assembly has been revealed recently. Septin filaments are essential for various cellular functions and their interaction with biological membranes or cytoskeleton components. However, the specific interaction between septins and their binding partners is still not well understood. In this study, the crucial role of the C-terminal domains in both septin polymerization and their association with the BD3 motif of the Borg family of Cdc42 effector proteins was described. It was found that the formation of a ternary complex stabilized the heterodimeric coiled coil formed by the C-terminal domains of septins and promoted filament formation under non-permissible conditions of ionic strength and protein concentration.

JOURNAL OF MOLECULAR BIOLOGY (2023)

Article Oncology

Deduction of CDC42EP3 suppress development and progression of osteosarcoma

Peng Xu et al.

Summary: This study found that CDC42EP3 is highly expressed in osteosarcoma and is associated with the progression of the disease. Knockdown of CDC42EP3 can inhibit tumor growth by suppressing proliferation, migration, and inducing apoptosis. Furthermore, CDC42EP3 knockdown can regulate the expression of epithelial and interstitial markers, as well as the PI3K/AKT/mTOR signaling pathway. Therefore, CDC42EP3 may be a potential target for osteosarcoma therapy.

EXPERIMENTAL CELL RESEARCH (2022)

Article Cell Biology

CDC42EP3 promotes glioma progression via regulation of CCND1

Zhigang Yang et al.

Summary: This study investigated the role of CDC42EP3 in glioma development and its potential downstream mechanism. It was found that CDC42EP3 overexpression was positively correlated with pathological grading and increased the risk of recurrence. Knocking down CDC42EP3 inhibited cell proliferation and migration while promoting apoptosis. The study also suggested that CDC42EP3 might regulate the expression of CCND1. Overall, CDC42EP3 was found to promote glioma progression through targeting CCND1.

CELL DEATH & DISEASE (2022)

Article Cell Biology

Human septins organize as octamer-based filaments and mediate actin-membrane anchoring in cells

Carla Silva Martins et al.

Summary: Septins are cytoskeletal proteins that form octamer-containing filaments and mediate actin-membrane anchoring, contributing to cell stiffness and mechanics.

JOURNAL OF CELL BIOLOGY (2022)

Article Multidisciplinary Sciences

Septins mediate a microtubule-actin crosstalk that enables actin growth on microtubules

Konstantinos Nakos et al.

Summary: Cellular morphogenesis and processes such as cell division and migration require the coordination of the microtubule and actin cytoskeletons. This study shows that septins mediate microtubule-actin crosstalk by coupling actin polymerization to microtubule lattices.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

Article Neurosciences

Right place, right time-Spatial guidance of neuronal morphogenesis by septin GTPases

Megan R. Radler et al.

Summary: Septins play a crucial role in neurogenesis by controlling membrane domain localization and regulating the cytoskeletal proteins to promote axon-dendrite formation and stability.

CURRENT OPINION IN NEUROBIOLOGY (2022)

Article Biochemistry & Molecular Biology

Cdc42-Borg4-Septin7 axis regulates HSC polarity and function

Ravinder Kandi et al.

Summary: The Cdc42-Borg4-Septin7 axis is crucial for maintaining polarity and function in HSCs, with genetic deletion of Borg4 or Septin7 resulting in reduced polarity frequency and engraftment potential of HSCs.

EMBO REPORTS (2021)

Article Cell Biology

Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse

Alexander Leithner et al.

Summary: Dendritic cells play a crucial role in the initiation of adaptive immunity by regulating the formation of immunological synapses with T cells through dynamic actin cytoskeletal rearrangements, demonstrating the importance of DC actin in immune synapse functionality.

JOURNAL OF CELL BIOLOGY (2021)

Article Biology

Generation of stress fibers through myosin-driven reorganization of the actin cortex

Jaakko Lehtimaki et al.

Summary: The study reveals that stress fibers can form without pre-existing actomyosin bundles, giving rise to structures known as cortical stress fibers, which are embedded in the cell cortex and assemble preferentially underneath the nucleus. The assembly process is orchestrated by non-muscle myosin II pulses, leading to the reinforcement of nascent focal adhesions and subsequent stabilization of the cortical stress fibers. These findings demonstrate a new mechanism for de novo generation of stress fibers from the actin cortex, highlighting the role of stochastic myosin pulses in the assembly of functional actomyosin bundles.
Article Oncology

CDC42EP3 promotes colorectal cancer through regulating cell proliferation, cell apoptosis and cell migration

Qiang Feng et al.

Summary: In this study, the role of CDC42EP3 in colorectal cancer (CRC) was investigated. The results showed that CDC42EP3 was significantly upregulated in CRC and its knockdown inhibited proliferation, colony formation, and migration, while promoting apoptosis of CRC cells. Furthermore, in vivo results confirmed that knockdown of CDC42EP3 attenuated tumor growth in CRC, indicating its potential as a target for innovative therapeutic approaches.

CANCER CELL INTERNATIONAL (2021)

Article Health Care Sciences & Services

Identification of Differentially Expressed Genes in Different Glioblastoma Regions and Their Association with Cancer Stem Cell Development and Temozolomide Response

Justin Bo-Kai Hsu et al.

Summary: The study identified potential target genes related to temozolomide (TMZ) resistance and glioblastoma multiforme (GBM) recurrence through differential gene expression analysis. Enrichment levels of specific genes in different tumor regions were found to be risk signatures for tumor recurrence, while other genes were identified as biomarkers for evaluating TMZ resistance. These findings offer new molecular strategies for GBM treatment.

JOURNAL OF PERSONALIZED MEDICINE (2021)

Article Oncology

CDC42EP3 is a key promoter involved in the development and progression of gastric cancer

Wenchao Chen et al.

Summary: The overexpression of CDC42EP3 in gastric cancer is positively correlated with tumor grade, while its knockdown inhibits cell proliferation and migration, promotes cell apoptosis, and suppresses tumor growth. Additionally, silencing CDC42EP3 was found to inhibit HSP27 and IGF-1sR expression and promote the expression of Caspase3, p53, TNF-alpha, TNF-beta, TRAILR-1, and TRAILR-2. CDC42EP3 acts as a tumor promoter in the development and progression of gastric cancer, making it a potential therapeutic target.

CARCINOGENESIS (2021)

Article Biochemistry & Molecular Biology

Cdc42 and its BORG2 and BORG3 effectors control the subcellular localization of septins between actin stress fibers and microtubules

Joelle Salameh et al.

Summary: This study demonstrates that cell resistance to taxanes involves the relocalization of septin from actin stress fibers to microtubules, which is triggered by acute paclitaxel treatment due to the release of Cdc42 effectors BORG2 and BORG3. Inhibiting Cdc42 leads to septin detachment from stress fibers and relocalization to microtubules, while overexpression of BORG2 or BORG3 retains septins on actin fibers even after paclitaxel treatment. These findings highlight the critical role of Cdc42, BORG2, and BORG3 in regulating the interplay between septins, actin fibers, and microtubules in response to taxanes.

CURRENT BIOLOGY (2021)

Article Multidisciplinary Sciences

Highly accurate protein structure prediction with AlphaFold

John Jumper et al.

Summary: Proteins are essential for life, and accurate prediction of their structures is a crucial research problem. Current experimental methods are time-consuming, highlighting the need for accurate computational approaches to address the gap in structural coverage. Despite recent progress, existing methods fall short of atomic accuracy in protein structure prediction.

NATURE (2021)

Review Neurosciences

Developmental and postdevelopmental roles of septins in the brain*

Natsumi Ageta-Ishihara et al.

Summary: Studies have revealed the crucial roles of the septin family in neural development, including involvement in neural progenitor cell proliferation, neurite development, synapse formation and regulation. The unexpected phenotypes from gain-and loss-of-function mutants suggest an unknown molecular network underlying pathogenetic processes of infectious diseases and neuropsychiatric disorders in humans.

NEUROSCIENCE RESEARCH (2021)

Article Multidisciplinary Sciences

Integrative bioinformatics and experimental analysis revealed down-regulated CDC42EP3 as a novel prognostic target for ovarian cancer and its roles in immune infiltration

Yuanliang Yan et al.

Summary: This study demonstrated the potential roles of m(6)A target gene CDC42EP3 in ovarian cancer, confirming its down-regulated expression in ovarian cancer tissues and cells. The lower expression of CDC42EP3 was correlated with poor prognosis in patients with ovarian cancer, and its expression was significantly associated with a diverse range of tumor-infiltrating immune cells.
Review Cell Biology

The Actin Cytoskeleton at the Immunological Synapse of Dendritic Cells

Jose Luis Rodriguez-Fernandez et al.

Summary: Dendritic cells are powerful antigen-presenting cells that control T cell activation through the immunological synapse. While most studies focus on the T cell side, dendritic cell side also plays a significant role in T cell activation, especially through actin polarization at the IS.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Review Biochemistry & Molecular Biology

Cellular functions of actin- and microtubule-associated septins

Elias T. Spiliotis et al.

Summary: Septins are key components of the cytoskeleton, interacting with actin filaments, microtubules, and membranes to regulate the organization and dynamics of the cytoskeletal networks essential for cellular morphogenesis. They play roles in cytokinesis, cell migration, and host defense against pathogens, with emerging functions at the interface of microtubules and membranes. Additionally, septins are involved in mitosis and meiosis, making them a unique module of cytoskeletal regulators with properties of actin-binding and microtubule-associated proteins.

CURRENT BIOLOGY (2021)

Article Oncology

The mutational landscape of early- and typical-onset oral tongue squamous cell carcinoma

Benjamin R. Campbell et al.

Summary: This study identified new and different driver genes for oral tongue cancer through international collaboration and data integration. Early-onset oral tongue cancer patients had a significantly lower mutation burden independent of tobacco use.

CANCER (2021)

Article Multidisciplinary Sciences

An atlas of the protein-coding genes in the human, pig, and mouse brain

Evelina Sjostedt et al.

SCIENCE (2020)

Article Medicine, Research & Experimental

Down-regulation of SEPT9 inhibits glioma progression through suppressing TGF-β-induced epithelial-mesenchymal transition (EMT)

Zhang Guodong et al.

BIOMEDICINE & PHARMACOTHERAPY (2020)

Article Oncology

The genomic profile of parathyroid carcinoma based on whole-genome sequencing

Ya Hu et al.

INTERNATIONAL JOURNAL OF CANCER (2020)

Article Cell Biology

CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion

Aaron J. Farrugia et al.

JOURNAL OF CELL BIOLOGY (2020)

Article Cell Biology

Regulation of microtubule plus end dynamics by septin 9

Konstantinos Nakos et al.

CYTOSKELETON (2019)

Article Mathematical & Computational Biology

Exome sequencing identifies predisposing and fusion gene in ganglioneuroma, ganglioneuroblastoma and neuroblastoma

Wei Wu et al.

MATHEMATICAL BIOSCIENCES AND ENGINEERING (2019)

Article Cell Biology

Cdc42 regulates the cellular localization of Cdc42ep1 in controlling neural crest cell migration

Shlomi Cohen et al.

JOURNAL OF MOLECULAR CELL BIOLOGY (2018)

Article Cell Biology

Septin-regulated actin dynamics promote Salmonella invasion of host cells

Kirsten C. Boddy et al.

CELLULAR MICROBIOLOGY (2018)

Review Biochemistry & Molecular Biology

Journey of siRNA: Clinical Developments and Targeted Delivery

Rahul R. Nikam et al.

NUCLEIC ACID THERAPEUTICS (2018)

Article Cell Biology

SUMOylation of human septins is critical for septin filament bundling and cytokinesis

David Ribet et al.

JOURNAL OF CELL BIOLOGY (2017)

Review Biochemistry & Molecular Biology

The Borg family of Cdc42 effector proteins Cdc42EP1-5

Aaron J. Farrugia et al.

BIOCHEMICAL SOCIETY TRANSACTIONS (2016)

Article Neurosciences

Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders?

Zhen Yan et al.

JOURNAL OF NEUROSCIENCE (2016)

Article Multidisciplinary Sciences

Septins guide microtubule protrusions induced by actin-depolymerizing toxins like Clostridium difficile transferase (CDT)

Thilo Noelke et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

Review Cell Biology

Septins and Bacterial Infection

Vincenzo Torraca et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2016)

Review Biochemistry & Molecular Biology

A biomechanical perspective on stress fiber structure and function

Elena Kassianidou et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2015)

Article Biochemistry & Molecular Biology

CEP2 Attenuates Myoblast Differentiation But Does Not Affect Proliferation

Ming Wu et al.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2015)

Article Biochemistry & Molecular Biology

Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity

Clayton Smith et al.

JOURNAL OF MOLECULAR BIOLOGY (2015)

Article Multidisciplinary Sciences

Genome-wide identification of zero nucleotide recursive splicing in Drosophila

Michael O. Duff et al.

NATURE (2015)

Review Neurosciences

Dendritic spine alterations in schizophrenia

Caitlin E. Moyer et al.

NEUROSCIENCE LETTERS (2015)

Article Biochemistry & Molecular Biology

JPred4: a protein secondary structure prediction server

Alexey Drozdetskiy et al.

NUCLEIC ACIDS RESEARCH (2015)

Article Multidisciplinary Sciences

Tissue-based map of the human proteome

Mathias Uhlen et al.

SCIENCE (2015)

Article Multidisciplinary Sciences

A CDC42EP4/septin-based perisynaptic glial scaffold facilitates glutamate clearance

Natsumi Ageta-Ishihara et al.

NATURE COMMUNICATIONS (2015)

Article Biochemistry & Molecular Biology

PhosphoSitePlus, 2014: mutations, PTMs and recalibrations

Peter V. Hornbeck et al.

NUCLEIC ACIDS RESEARCH (2015)

Article Microbiology

Off-Target Effects of the Septin Drug Forchlorfenuron on Nonplant Eukaryotes

Lydia R. Heasley et al.

EUKARYOTIC CELL (2014)

Article Biochemistry & Molecular Biology

Phosphorylation of Cdc42 Effector Protein-4 (CEP4) by Protein Kinase C Promotes Motility of Human Breast Cells

Xin Zhao et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

Article Biochemical Research Methods

Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics

Linn Fagerberg et al.

MOLECULAR & CELLULAR PROTEOMICS (2014)

Article Multidisciplinary Sciences

A Septin-Dependent Diffusion Barrier at Dendritic Spine Necks

Helge Ewers et al.

PLOS ONE (2014)

Article Multidisciplinary Sciences

Septin assemblies form by diffusion-driven annealing on membranes

Andrew A. Bridges et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

Article Biotechnology & Applied Microbiology

SOAPfuse: an algorithm for identifying fusion transcripts from paired-end RNA-Seq data

Wenlong Jia et al.

GENOME BIOLOGY (2013)

Article Medicine, Research & Experimental

Genes responsible for the characteristics of primary cultured invasive phenotype hepatocellular carcinoma cells

Zu-Yau Lin et al.

BIOMEDICINE & PHARMACOTHERAPY (2012)

Article Cell Biology

Actin stress fibers - assembly, dynamics and biological roles

Sari Tojkander et al.

JOURNAL OF CELL SCIENCE (2012)

Review Biochemistry & Molecular Biology

Septin roles in tumorigenesis

Diana Connolly et al.

BIOLOGICAL CHEMISTRY (2011)

Article Multidisciplinary Sciences

A conditional knockout resource for the genome-wide study of mouse gene function

William C. Skarnes et al.

NATURE (2011)

Article Biochemistry & Molecular Biology

Phosphatidylinositol-4,5-bisphosphate Promotes Budding Yeast Septin Filament Assembly and Organization

Aurelie Bertin et al.

JOURNAL OF MOLECULAR BIOLOGY (2010)

Article Cell & Tissue Engineering

A Role for Borg5 During Trophectoderm Differentiation

Queenie P. Vong et al.

STEM CELLS (2010)

Article Microscopy

Mechanisms of actin stress fibre assembly

P. Naumanen et al.

JOURNAL OF MICROSCOPY (2008)

Article Cell Biology

Protein networks supporting AP-3 function in targeting lysosomal membrane proteins

Thorsten Baust et al.

MOLECULAR BIOLOGY OF THE CELL (2008)

Article Biochemistry & Molecular Biology

Role of septin cytoskeleton in spine morphogenesis and dendrite development in neurons

Tomoko Tada et al.

CURRENT BIOLOGY (2007)

Article Biochemistry & Molecular Biology

The GTP-binding protein septin 7 is critical for dendrite branching and dendritic-spine morphology

Yunli Xie et al.

CURRENT BIOLOGY (2007)

Article Cell Biology

Stress fibers are generated by two distinct actin assembly mechanisms in motile cells

P Hotulainen et al.

JOURNAL OF CELL BIOLOGY (2006)

Article Cell Biology

Functional interdependence between septin and actin cytoskeleton

K Schmidt et al.

BMC CELL BIOLOGY (2004)

Article Biochemistry & Molecular Biology

Filament formation of MSF-A, a mammalian septin, in human mammary epithelial cells depends on interactions with microtubules

K Nagata et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2003)

Article Biochemistry & Molecular Biology

Borg/septin interactions and the assembly of mammalian septin heterodimers, trimers, and filaments

PJ Sheffield et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2003)

Article Cell Biology

Borg proteins control septin organization and are negatively regulated by Cdc42

G Joberty et al.

NATURE CELL BIOLOGY (2001)

Article Biochemistry & Molecular Biology

A new family of Cdc42 effector proteins, CEPs, function in fibroblast and epithelial cell shape changes

DS Hirsch et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2001)