Article
Biochemistry & Molecular Biology
Xin Zhu, Jieling Wang, Shufen Li, Karl Lechtreck, Junmin Pan
Summary: This study revealed that the IFT-B protein IFT54 interacts with both kinesin-II and IFT dynein, regulating anterograde transport. Deletions of specific residues in IFT54 resulted in disrupted anterograde trafficking of IFT, with accumulations of IFT motors and complexes in different regions of cilia. This suggests a central role for IFT54 in binding IFT motors during anterograde transport.
Review
Cell Biology
Nikolai Klena, Gaia Pigino
Summary: Cilia are eukaryotic organelles that play a crucial role in cell motility and signaling. Recent advances in cryo-electron tomography and single-particle analysis cryo-electron microscopy have provided important insights into the structure and function of cilia.
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Xiaowen Huang, Aifang Li, Peng Xu, Yangfan Yu, Shuxuan Li, Lina Hu, Shuying Feng
Summary: Extracellular vesicles (EVs) show promise as a gene delivery platform for targeted CRISPR/Cas systems, overcoming challenges associated with toxicity and immunogenicity. This review explores strategies to improve loading capacity, safety, stability, targeting, and tracking for EV-based CRISPR/Cas delivery. It hypothesizes future avenues for EV-based delivery systems to bridge the gap between gene editing technologies and gene therapies.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Developmental Biology
Daniel C. Quesnelle, Cindy Huang, Jeffrey R. Boudreau, Annie Lam, Jadine Paw, William G. Bendena, Ian D. Chin-Sang
Summary: Cells undergo strict regulation in morphogenesis, and mutations in vab genes of Caenorhabditis elegans cause morphological defects. The function of the vab-6 gene, however, remained unknown. Here, we found that vab-6 is a subunit of the kinesin-II heterotrimeric motor complex called klp-20/Kif3a, which is involved in developing sensory cilia. Mutant versions of KLP-20 protein cause a bumpy epidermal phenotype, indicating its role in regulating epidermal morphogenesis.
DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Shunya Hiyamizu, Hantian Qiu, Laura Vuolo, Nicola L. Stevenson, Caroline Shak, Kate J. Heesom, Yuki Hamada, Yuta Tsurumi, Shuhei Chiba, Yohei Katoh, David J. Stephens, Kazuhisa Nakayama
Summary: The dynein-2 complex is transported anterogradely within cilia to drive retrograde trafficking of the intraflagellar transport (IFT) machinery containing IFT-A and IFT-B complexes. There are multiple interactions between the dynein-2 and IFT-B subunits, including WDR60 and the DYNC2H1-DYNC2LI1 dimer from dynein-2, and IFT54 and IFT57 from IFT-B. These interactions play a crucial role in the connection between dynein-2 and IFT-B.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biology
Adria Razzauti, Patrick Laurent
Summary: Cilia are sensory organelles protruding from cell surfaces that can release extracellular vesicles (EVs) in some organisms. These EVs are formed by ciliated sensory neurons, with release from both the cilia tip and periciliary membrane compartment. The formation and release of EVs help maintain cilia composition.
Article
Oncology
Nihar Godbole, Alexander Quinn, Flavio Carrion, Emanuele Pelosi, Carlos Salomon
Summary: Ovarian Cancer (OC) is the eighth most diagnosed cancer in females worldwide and ranks as the fifth leading cause of cancer-related mortality among patients globally. CRISPR-Cas-based genome editing has shown potential for treating various diseases, but the challenge lies in finding an optimal vehicle for delivering CRISPR molecular machinery into target cells or tissues. Recently, extracellular vesicles (EVs) have emerged as potential delivery vehicles due to their ability to shield molecular cargo and cross biological barriers.
SEMINARS IN CANCER BIOLOGY
(2023)
Article
Biology
Shunya Hiyamizu, Hantian Qiu, Yuta Tsurumi, Yuki Hamada, Yohei Katoh, Kazuhisa Nakayama
Summary: The dynein-2 complex within cilia needs to be transported as an anterograde cargo to enable its function in retrograde trafficking. Previous research has shown that interaction of multiple IFT-B subunits, including IFT54, with WDR60 and the DYNC2H1-DYNC2LI1 dimer of dynein-2 is necessary for the trafficking of dynein-2. However, deleting the IFT54-binding site from WDR60 only has a minor effect on dynein-2 trafficking and function. The results suggest that the C-terminal coiled-coil region of IFT54 is essential for IFT-B function, and the middle linker region of IFT54 is required for ciliary retrograde trafficking by mediating the binding of IFT-B to the dynein-2 complex.
Review
Physics, Multidisciplinary
Swayamshree Patra, Debashish Chowdhury, Frank Juelicher
Summary: This review examines the transport logistics and mechanisms of length control of cell protrusions, as well as coordination among multiple appendages. A case study on the eukaryotic flagellum is presented, showcasing the extensively studied flagellar length control mechanisms. Brief discussions on non-flagellar cell protrusions provide a glimpse into the challenging frontiers of research on subcellular length control phenomena.
PHYSICS REPORTS-REVIEW SECTION OF PHYSICS LETTERS
(2022)
Article
Genetics & Heredity
Felix Hoffmann, Sylvia Bolz, Katrin Junger, Franziska Klose, Timm Schubert, Franziska Woerz, Karsten Boldt, Marius Ueffing, Tina Beyer
Summary: This study reveals the redundancy of TTC30A and TTC30B in intraflagellar transport (IFT) and their critical role in cilium formation. The loss of either paralogue can be compensated by the other, preventing severe ciliary defects. However, a complete loss of both paralogues leads to a severe ciliogenesis defect with no cilia formation.
Article
Chemistry, Multidisciplinary
Xiao Liu, Zhengcong Cao, Weizhong Wang, Cheng Zou, Yingwen Wang, Luxiang Pan, Bo Jia, Kuo Zhang, Wangqian Zhang, Weina Li, Qiang Hao, Yingqi Zhang, Wei Zhang, Xiaochang Xue, Wei Lin, Meng Li, Jintao Gu
Summary: This study identified glutathione synthetase (GSS) as a potential regulator of radioresistance in glioblastoma (GBM) through in vivo loss-of-function genome-wide CRISPR screening and transcriptome analyses. High GSS levels were associated with poor prognosis and relapse in glioma patients. The study also developed a gene editing delivery system that could target the blood-brain barrier (BBB) and tumor for potential therapeutic translation.
Article
Oncology
Andrew Chin, Javier Mariscal, Minhyung Kim, Giorgia Guerra, Blandine Victor, Chen Qian, Elisabetta Broseghini, Edwin Posadas, Michael R. Freeman, Shivani Sharma, Paolo Gandellini, Nadia Zaffaroni, Sungyong You, Keith Syson Chan, Jlenia Guarnerio, Muller Fabbri, Dolores Di Vizio
Summary: This study reveals a novel mechanism of extracellular vesicles (EVs) shedding, in which the inhibition of SEC23A by miR-1227 induces a shift in EV shedding, favoring the shedding of large EV over small EV.
Article
Biochemistry & Molecular Biology
Darja Bozic, Matej Hocevar, Matic Kisovec, Manca Pajnic, Ljubisa Paden, Marko Jeran, Apolonija Bedina Zavec, Marjetka Podobnik, Ksenija Kogej, Ales Iglic, Veronika Kralj-Iglic
Summary: EVs have potential in diagnostics and therapy, but poor reproducibility in studies hinders practical application. Study on hbEVs stability reveals consistent morphology under specific conditions, making them suitable as EV reference material.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Xuting Zhou, Wenting Tang, Yan Zhang, Aidong Deng, Yuehua Guo, Li Qian
Summary: A sensitive in situ detection strategy for exosomal miR-1246 has been developed by integrating the CRISPR/Cas13a system with liposomes, allowing for quantitative response to exosomal miR-1246 concentration and potential applications in breast cancer patient detection and early disease differentiation.
Article
Cell Biology
Francisco Goncalves-Santos, Ana R. G. De-Castro, Diogo R. M. Rodrigues, Maria J. G. De-Castro, Reto Gassmann, Carla M. C. Abreu, Tiago J. Dantas
Summary: This study investigates the impact of disabling the autoinhibition mechanism of dynein-2 on intraflagellar transport (IFT) using genome editing techniques in Caenorhabditis elegans. The results show that retrograde transport can be reactivated in IFT-A-deficient cilia by activating dynein-2 using a "hot-wiring" approach, providing functional evidence for dynein-2 autoinhibition during anterograde IFT and establishing key roles for IFT-A in regulating retrograde transport.
Article
Cell Biology
Takuya Kobayashi, Yamato Ishida, Tomoaki Hirano, Yohei Katoh, Kazuhisa Nakayama
Summary: The study demonstrates the important role of IFT-A's IFT144-IFT122 and IFT-B's IFT88-IFT52 in mediating ciliary transport through their cooperation, facilitating the entry of GPCRs and retrograde trafficking of the IFT machinery from the ciliary tip.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Biology
Hantian Qiu, Sayaka Fujisawa, Shohei Nozaki, Yohei Katoh, Kazuhisa Nakayama
Summary: The binding of INPP5E to ARL13B is crucial for its steady-state localization on the ciliary membrane, but is not necessary for its entry into cilia.
Article
Biochemistry & Molecular Biology
Taro Chaya, Hiroshi Ishikane, Leah R. Varner, Yuko Sugita, Yamato Maeda, Ryotaro Tsutsumi, Daisuke Motooka, Daisuke Okuzaki, Takahisa Furukawa
Summary: The study found that variants in the CYFIP2 gene may lead to early-onset epileptic encephalopathy, developmental delay, and intellectual disability. Deficiency in Cyfip2 affects retinal and visual functions, impairing visual function at the organismal level.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Hantian Qiu, Yuta Tsurumi, Yohei Katoh, Kazuhisa Nakayama
Summary: It has been discovered that pathogenic DYNC2LI1 deletion variants are compromised in their ability to interact with DYNC2H1 and WDR60, and cause ciliary defects when coexpressed with a missense variant that mimics the situation of compound heterozygous ciliopathy cells.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Caroline Shak, Laura Vuolo, Borhan Uddin, Yohei Katoh, Tom Brown, Aakash G. Mukhopadhyay, Kate Heesom, Anthony J. Roberts, Nicola Stevenson, Kazuhisa Nakayama, David J. Stephens
Summary: The primary cilium is a sensory organelle that receives signals from the external environment and transports them into the cell. Mutations in proteins required for transport in the primary cilium result in ciliopathies, which lead to the malformation of organs and skeletal dysplasias. WDR34, a dynein-2 intermediate chain, is necessary for the maintenance of cilia function.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cell Biology
Yuuki Satoda, Tatsuro Noguchi, Taiju Fujii, Aoi Taniguchi, Yohei Katoh, Kazuhisa Nakayama
Summary: Primary cilia are crucial for tissue morphogenesis and contain specific proteins. The study shows that CCRK, BROMI, FAM149B1, and probably CFAP20 together regulate the intraflagellar transport (IFT) machinery and are controlled by ICK. Defects in CCRK, BROMI, and FAM14981 result in abnormally long cilia and accumulation of IFT machinery and ICK at the ciliary tip.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Cell Biology
Zhuang Zhou, Yohei Katoh, Kazuhisa Nakayama
Summary: The intraflagellar transport (IFT) machinery and RABL2 GTPase play important roles in regulating ciliary function. This study reveals the interaction between RABL2 and the IFT-B complex, shedding light on the regulatory mechanisms of ciliary protein trafficking.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Cell Biology
Yamato Ishida, Koshi Tasaki, Yohei Katoh, Kazuhisa Nakayama
Summary: Mutations in IFT52 lead to impaired protein trafficking within cilia, resulting in skeletal ciliopathies.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Cell Biology
Shunya Hiyamizu, Hantian Qiu, Laura Vuolo, Nicola L. Stevenson, Caroline Shak, Kate J. Heesom, Yuki Hamada, Yuta Tsurumi, Shuhei Chiba, Yohei Katoh, David J. Stephens, Kazuhisa Nakayama
Summary: The dynein-2 complex is transported anterogradely within cilia to drive retrograde trafficking of the intraflagellar transport (IFT) machinery containing IFT-A and IFT-B complexes. There are multiple interactions between the dynein-2 and IFT-B subunits, including WDR60 and the DYNC2H1-DYNC2LI1 dimer from dynein-2, and IFT54 and IFT57 from IFT-B. These interactions play a crucial role in the connection between dynein-2 and IFT-B.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biology
Shunya Hiyamizu, Hantian Qiu, Yuta Tsurumi, Yuki Hamada, Yohei Katoh, Kazuhisa Nakayama
Summary: The dynein-2 complex within cilia needs to be transported as an anterograde cargo to enable its function in retrograde trafficking. Previous research has shown that interaction of multiple IFT-B subunits, including IFT54, with WDR60 and the DYNC2H1-DYNC2LI1 dimer of dynein-2 is necessary for the trafficking of dynein-2. However, deleting the IFT54-binding site from WDR60 only has a minor effect on dynein-2 trafficking and function. The results suggest that the C-terminal coiled-coil region of IFT54 is essential for IFT-B function, and the middle linker region of IFT54 is required for ciliary retrograde trafficking by mediating the binding of IFT-B to the dynein-2 complex.
Article
Biochemistry & Molecular Biology
Koshi Tasaki, Zhuang Zhou, Yamato Ishida, Yohei Katoh, Kazuhisa Nakayama
Summary: Due to their important roles in development and homeostasis, defects in cilia lead to ciliopathies with various clinical manifestations. The intraflagellar transport (IFT) machinery, consisting of IFT-A and IFT-B complexes, is responsible for intraciliary trafficking as well as import and export of ciliary proteins. The BBSome, composed of eight subunits encoded by causative genes of Bardet-Biedl syndrome (BBS), links the IFT machinery to ciliary membrane proteins to facilitate their export from cilia. Mutations in IFT-B subunits, including IFT81, can cause skeletal ciliopathies by disrupting the interactions among IFT-B subunits and impairing ciliogenesis and ciliary protein trafficking.
HUMAN MOLECULAR GENETICS
(2023)