Article
Cell Biology
Hankyu Lee, Kyeong-Hye Moon, Jieun Song, Suyeon Je, Jinwoong Bok, Hyuk Wan Ko
Summary: Primary cilia play essential roles as signaling centers during development and adult homeostasis. Disruption of ciliary structure or function causes congenital human disorders. This study reveals the important roles of centriolar distal appendage (DAP) proteins in ciliogenesis and animal development. The findings also indicate the tissue-specific differential requirement of DAPs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elena X. Wang, Jacob S. Turner, David L. Brautigan, Zheng Fu
Summary: In this study, we identified a small molecular inhibitor called Alvocidib that can potently inhibit CILK1, promote cilia elongation, and selectively inhibit other protein kinases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Huijie Zhao, Ziam Khan, Christopher J. Westlake
Summary: Ciliogenesis is a complex process involved in the assembly of cilia and flagella, which are essential for cell motility and signaling. Membrane trafficking regulators play a crucial role in ciliogenesis by organizing membranes around microtubule-based structures. The association of membranes with the distal end of the centriole is a critical step in initiating ciliogenesis. This review focuses on recent insights into cilia biogenesis and the roles of membrane trafficking regulators in ciliogenesis mechanisms relevant to human disease.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Biology
Xiaoyu Tian, Huijie Zhao, Jun Zhou
Summary: The BBSome is an octameric protein complex that regulates ciliary transport and signaling. Mutations in BBSome subunits are closely associated with ciliary defects and lead to ciliopathies, notably Bardet-Biedl syndrome. An improved understanding of BBSome-mediated biological events and molecular mechanisms is expected to help advance the development of diagnostic and therapeutic approaches for BBSome-related diseases.
Review
Anatomy & Morphology
Sara P. Abraham, Alexandru Nita, Pavel Krejci, Michaela Bosakova
Summary: Primary cilia are dynamic compartments that regulate various aspects of cellular signaling, including skeletal development and homeostasis. Skeletal ciliopathies are genetic disorders with a wide range of pathologies, and protein kinases in cilia play essential roles in bone physiology signaling pathways.
DEVELOPMENTAL DYNAMICS
(2022)
Review
Cell Biology
Sarah K. Suciu, Tamara Caspary
Summary: Neural development involves a series of cellular events including cell specification, proliferation, and migration, with anomalies potentially leading to malformation of the nervous system. The primary cilium plays a critical role in neurodevelopment, with mutations in cilia-associated proteins causing human diseases and highlighting the essential nature of cilia in multiple neural processes. Further research is needed to explore the potential roles of cilia regulation in neural development and whether cilia-associated proteins function outside the cilium in certain aspects of neurodevelopment.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Roberto Quadri, Sarah Sertic, Anna Ghilardi, Diego Rondelli, Guido Roberto Gallo, Luca Del Giacco, Marco Muzi-Falconi
Summary: The study identified an atypical protein kinase, Haspin, as a key regulator of primary cilia dynamics, showing that its activity is essential for the relocation of Dido3-HDAC6 to the basal body, affecting cilia length determination and maintenance. This novel mechanism sheds light on the intricate processes governing primary cilia homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Thuy N. Vien, My C. Ta, Louise F. Kimura, Tuncer Onay, Paul G. DeCaen
Summary: In this study, the researchers found that PKD2L1 localizes and functions as a Ca2+ channel in the primary cilia of hippocampal neurons. Loss of PKD2L1 expression disrupts primary ciliary maturation, weakens neuronal high-frequency excitability, and leads to seizure susceptibility and autism spectrum disorder-like behavior in mice. The disproportionate impairment of interneuron excitability suggests that circuit disinhibition underlies the neurophenotypic features of these mice. These findings identify PKD2L1 channels as regulators of hippocampal excitability and the neuronal primary cilia as organelle mediators of brain electrical signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Behavioral Sciences
Chao Xie, Jeffrey R. Martens
Summary: Olfactory dysfunction is a common disorder with various causes, including ciliopathies. Although there is currently no specific treatment for olfactory dysfunction caused by ciliopathies, targeted gene replacement shows promise as a potential therapeutic option. Further research is needed to develop alternative therapeutic targets for broader curative measures in ciliopathies.
Article
Food Science & Technology
Marina Murillo-Pineda, Juan M. Coto-Cid, Maria Romero, Jesus G. Zorrilla, Nuria Chinchilla, Zahara Medina-Calzada, Rosa M. Varela, Alvaro Juarez-Soto, Francisco A. Macias, Elena Reales
Summary: This study evaluated the effects of certain plant-derived metabolites, sesquiterpene lactones (SLs), on primary cilia. It was found that SLs disrupted the formation of primary cilia, except for grosheimin which actually stabilized and promoted the formation of primary cilia.
Review
Cell Biology
Nan-Xi Zheng, Ya-Ting Miao, Xi Zhang, Mu-Zhi Huang, Muhammad Jahangir, Shilin Luo, Bing Lang
Summary: Cilium is a conserved antenna-like structure on mammalian cells, and dysfunctional primary cilia are associated with various congenital diseases. Intraflagellar transport (IFT) is essential for maintaining cilia function, and disrupted IFT contributes to ciliopathies. IFT172 is a newly identified protein related to rare ciliopathies such as MZSDS and BBS, and this review summarizes its genetic and protein characteristics and its role in intraflagellar transport.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Developmental Biology
Kelsey H. Elliott, Sai K. Balchand, Christian Louis Bonatto Paese, Ching-Fang Chang, Yanfen Yang, Kari M. Brown, Daniel T. Rasicci, Hao He, Konrad Thorner, Praneet Chaturvedi, Stephen A. Murray, Jing Chen, Aleksey Porollo, Kevin A. Peterson, Samantha A. Brugmann
Summary: This study provides a searchable transcriptomic resource for the primary ciliome, revealing differentially expressed genes with tissue and temporal specificity. The genes within the differentially expressed ciliome show a lower level of functional constraint across species, indicating organism and cell-specific functional adaptation. The functional validation of ciliary heterogeneity was performed by disrupting ciliary genes using Cas9 gene editing, which exhibited dynamic gene expression profiles during osteogenic differentiation of multipotent neural crest cells. Overall, this novel primary cilia-focused resource allows researchers to explore the correlation between tissue and cell-type specific functions, ciliary heterogeneity, and the range of phenotypes associated with ciliopathies.
Article
Cell Biology
Zachariah E. Hale, Junichi Sadoshima
Summary: Primary cilia play a significant role in congenital heart disease and cardiac pathology. The loss of primary cilia function has been linked to heart failure and other cardiovascular abnormalities. Further research is needed to explore the specific mechanisms of primary cilia in adult cardiac pathology, especially heart failure.
Review
Cell Biology
Holly Y. Chen, Ryan A. Kelley, Tiansen Li, Anand Swaroop
Summary: The primary cilium is a microtubule-based organelle that senses external environment and modulates diverse signaling pathways in different cell types and tissues; ciliopathies are a spectrum of clinical entities caused by aberrant ciliogenesis or ciliary transport, leading to overlapping yet highly variable phenotypes; dysfunction and degeneration of light sensing photoreceptors in the retina are highly penetrant in ciliopathies.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Toneisha Stubbs, Andrew Koemeter-Cox, James I. Bingman, Fangli Zhao, Anuradha Kalyanasundaram, Leslie A. Rowland, Muthu Periasamy, Calvin S. Carter, Val C. Sheffield, Candice C. Askwith, Kirk Mykytyn
Summary: A rod-shaped appendage called a primary cilium projects from most central neurons in the mammalian brain. Cilia are important for neuronal signaling and their dysfunction is associated with various neuropathologies. This study demonstrates that disrupting the localization of a specific ciliary GPCR, called dopamine receptor 1 (D-1), in neurons leads to obesity and reduced locomotor activity in male and female mice. Loss of a BBS protein or cilia on D-1-expressing neurons also reduces D-1-mediated signaling. These findings highlight the importance of neuronal cilia for proper GPCR signaling and shed light on the role of cilia in regulating weight and locomotor activity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell Biology
Yoon Seon Oh, Eric J. Wang, Casey D. Gailey, David L. Brautigan, Benjamin L. Allen, Zheng Fu
Review
Biochemistry & Molecular Biology
Zheng Fu, Casey D. Gailey, Eric J. Wang, David L. Brautigan
Article
Cell Biology
Eric J. Wang, Casey D. Gailey, David L. Brautigan, Zheng Fu
Article
Cell Biology
James T. O'Connor, Aaron C. Stevens, Erica K. Shannon, Fabiha Bushra Akbar, Kimberly S. LaFever, Neil P. Narayanan, Casey D. Gailey, M. Shane Hutson, Andrea Page-McCaw
Summary: Research shows that wounds in the Drosophila notum trigger an increase in cytoplasmic calcium by activating extracellular cytokines Gbps, which then signal surrounding epithelial cells through Mthl10 receptors.
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Kathryn A. Salvati, Ashley J. Mason, Casey D. Gailey, Eric J. Wang, Zheng Fu, Mark P. Beenhakker
Summary: The study found that mice carrying mutations in the Cilk1 gene did not exhibit epilepsy, suggesting that the link between CILK1 mutations and JME is not through haploinsufficiency of CILK1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Elena X. Wang, Jacob S. Turner, David L. Brautigan, Zheng Fu
Summary: In this study, we identified a small molecular inhibitor called Alvocidib that can potently inhibit CILK1, promote cilia elongation, and selectively inhibit other protein kinases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jacob S. Turner, Ellie A. Mccabe, Kevin W. Kuang, Casey D. Gailey, David L. Brautigan, Ana Limerick, Elena X. Wang, Zheng Fu
Summary: CILK1 kinase interacts with KATNIP to enhance its activity and cellular signaling, thereby regulating the growth and development of primary cilia.
MOLECULAR AND CELLULAR BIOLOGY
(2023)