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
Biochemistry & Molecular Biology
Chao Xie, Julien C. Habif, Cedric R. Uytingco, Kirill Ukhanov, Lian Zhang, Carlos de Celis, Val C. Sheffield, Jeffrey R. Martens
Summary: Bardet-Biedl syndrome (BBS) is a hereditary genetic disorder that leads to various clinical manifestations, including olfactory dysfunction. A study using a mouse model found that the olfactory system of Bbs1(M390R/M390R) mice was significantly affected, but their odor discrimination acuity was still well maintained. Adenoviral expression of Bbs1 in olfactory sensory neurons can restore olfactory system function.
Article
Multidisciplinary Sciences
Rui-Kai Zhang, Wei-Yue Sun, Yan-Xia Liu, Emma Y. Zhang, Zhen-Chuan Fan
Summary: This study reveals the mechanism of signal protein export from cilia via the RABL2-ARL3 cascade-mediated outward BBSome transition zone diffusion pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Yan-Xia Liu, Wen -Juan Li, Rui-Kai Zhang, Sheng-Nan Sun, Zhen-Chuan Fan
Summary: Certain ciliary signaling proteins are transported from the tip to the base of cilia via retrograde intraflagellar transport (IFT), facilitated by the BBSome and ARL13. The interaction between ARL13GTP and BBS3GTP at the ciliary tip plays a crucial role in properly coupling the BBSome with signaling cargo. This understanding provides mechanistic insights into the defects seen in hedgehog signaling in humans with ARL13b and BBS3 mutations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Toneisha Stubbs, James I. Bingman, Jason Besse, Kirk Mykytyn
Summary: Primary cilia are important for neuronal functions and their dysfunction is linked to ciliopathies. Bardet-Biedl syndrome proteins play a crucial role in trafficking G protein-coupled receptors (GPCRs) in neuronal cilia, and their absence leads to abnormal localization of signaling proteins in the brain.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Genetics & Heredity
Urszula Smyczynska, Marcin Stanczak, Miljan Kuljanin, Aneta Wlodarczyk, Ewelina Stoczynska-Fidelus, Joanna Taha, Bartlomiej Pawlik, Maciej Borowiec, Joseph D. D. Mancias, Wojciech Mlynarski, Piotr Rieske, Wojciech Fendler, Agnieszka Zmyslowska
Summary: This study conducted transcriptomic and proteomic analysis on cellular models of Alstrom syndrome and Bardet-Biedl syndrome, identifying common and distinct pathological mechanisms between the two syndromes. Genes related to lipid and glycosaminoglycan metabolism and small molecule transport were downregulated, while those associated with signal transduction, immune system, cell cycle control, and DNA replication and repair were upregulated. Protein pathways involved in autophagy, apoptosis, cilium assembly, and Gli1 protein were also upregulated in both syndromes.
Article
Multidisciplinary Sciences
Alexander Ewerling, Vanessa Maissl, Bill Wickstead, Helen Louise May-Simera
Summary: The BBSome, a transport complex in cilia, also has nuclear functions. These functions are not restricted to mammals and may be a common feature in eukaryotes.
Review
Ophthalmology
Bharatendu Chandra, Moon Ley Tung, Ying Hsu, Todd Scheetz, Val C. Sheffield
Summary: The primary cilium is a specialized organelle in eukaryotes that plays an important role in cell signaling and transportation. Ciliopathies are a group of disorders caused by ciliary dysfunction or abnormal ciliogenesis, with multiorgan involvement. Understanding the genetics and clinical features of ciliopathies, such as Bardet-Biedl syndrome, is challenging but crucial for therapeutic development. This review discusses the structure and function of primary cilia, their role in retinal photoreceptors, and the progress made in understanding ciliopathies.
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
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
Endocrinology & Metabolism
Yanzhen Zhang, Lidan Zhang, Sufang Sun, Li Wen, Yongmiao Pan
Summary: This study reported a patient with BBS12 syndrome, caused by a de novo mutation inherited from the mother, and a heterozygous mutation and deletion inherited from the father.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2022)
Review
Genetics & Heredity
Xin-Yi Zou, Yang-Li Dai, Ling-Hui Zeng
Summary: This study analyzed the phenotypes, genotypes, and the relationship between phenotypes and genotypes in Chinese patients with Bardet-Biedl syndrome (BBS). It found that misdiagnosis or missed diagnosis of BBS is common in China, and BBS should be considered in patients with specific symptoms or in fetuses with certain deformities. Genetic analysis is crucial for early diagnosis.
FRONTIERS IN GENETICS
(2023)
Article
Cell Biology
Lena Bruecker, Stefanie Kornelia Becker, Vanessa Maissl, Gregory Harms, Maddy Parsons, Helen Louise May-Simera
Summary: Primary cilia are important for cellular communication and defects in cilia development or function are associated with genetic disorders. Recent research suggests that ciliary proteins are involved in actin regulation, but the exact nature of their interconnection is not fully understood.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2023)
Article
Cell Biology
Jin Dai, Gui Zhang, Rama A. Alkhofash, Betlehem Mekonnen, Sahana Saravanan, Bin Xue, Zhen-Chuan Fan, Ewelina Betleja, Douglas G. Cole, Peiwei Liu, Karl Lechtreck
Summary: The loss of Chlamydomonas ARL13 impedes BBSome-dependent protein transport, resulting in overlapping biochemical defects in arl13 and bbs mutant cilia.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Deng-Fu Guo, Ronald A. Merrill, Lan Qian, Ying Hsu, Qihong Zhang, Zhihong Lin, Daniel R. Thedens, Yuriy M. Usachev, Isabella Grumbach, Val C. Sheffield, Stefan Strack, Kamal Rahmouni
Summary: The study reveals that the BBSome protein complex plays a critical role in regulating mitochondrial dynamics and function. The disruption of the BBSome leads to excessive fusion of mitochondria in various cell types, and this morphological change is associated with functional abnormalities, including reduced oxygen consumption rate and altered mitochondrial distribution and calcium handling. Mechanistically, the BBSome modulates the activity of the key regulator protein DRP1 through regulating its phosphorylation and translocation, and rescuing the decrease in DRP1 activity can normalize the defects induced by BBSome deficiency.
MOLECULAR METABOLISM
(2023)
Article
Multidisciplinary Sciences
Jieling Wang, Xin Zhu, Zhengmao Wang, Xuecheng Li, Hui Tao, Junmin Pan
Summary: The machinery of intraflagellar transport (IFT) consists of IFT motors and cargo adaptors, including IFT-A and IFT-B complexes. This study reveals the role of IFT38 in the regulation of anterograde IFT and retrograde trafficking of BBSome. The stability of IFT-B1 and IFT-B2 is mutually dependent and mediated by the connecting tetramer IFT38/5788/52. The findings suggest a modular pathway for IFT-B assembly.
Review
Biochemistry & Molecular Biology
Cedric R. Uytingco, Warren W. Green, Jeffrey R. Martens
CURRENT MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Sangram Gore, Kirill Ukhanov, Cyril Herbivo, Naeem Asad, Yuriy Bobkov, Jeffrey R. Martens, Timothy M. Dore
ACS CHEMICAL BIOLOGY
(2020)
Review
Behavioral Sciences
Timothy S. McClintock, Naazneen Khan, Chao Xie, Jeffrey R. Martens
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
Cell Biology
Kirill Ukhanov, Cedric Uytingco, Warren Green, Lian Zhang, Stephane Schurmans, Jeffrey R. Martens
Summary: The lipid composition of the cilia membrane plays a critical role in cilia formation, maintenance and function. Deletion of a specific gene leads to remodeling of ciliary phospholipids and elongation of cilia, impacting odor adaptation and response kinetics. Gene replacement restores ciliary localization and odor response kinetics.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Chao Xie, Julien C. Habif, Cedric R. Uytingco, Kirill Ukhanov, Lian Zhang, Carlos de Celis, Val C. Sheffield, Jeffrey R. Martens
Summary: Bardet-Biedl syndrome (BBS) is a hereditary genetic disorder that leads to various clinical manifestations, including olfactory dysfunction. A study using a mouse model found that the olfactory system of Bbs1(M390R/M390R) mice was significantly affected, but their odor discrimination acuity was still well maintained. Adenoviral expression of Bbs1 in olfactory sensory neurons can restore olfactory system function.
Article
Medicine, Research & Experimental
Chao Xie, Julien C. Habif, Kirill Ukhanov, Cedric R. Uytingco, Lian Zhang, Robert J. Campbell, Jeffrey R. Martens
Summary: Ciliopathies are a class of genetic diseases that cause dysfunction in cilia in multiple organ systems, including the olfactory system. This study investigates the mechanism behind the reduction of olfactory cilia in ciliopathy Bardet-Biedl syndrome (BBS) and finds that phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and F-actin play important roles in cilia shortening. The researchers successfully restored cilia length and rescued odor detection and perception in BBS using a gene therapeutic approach. These findings provide valuable insights for the treatment of ciliopathies.
Article
Developmental Biology
Julien C. Habif, Chao Xie, Carlos de Celis, Kirill Ukhanov, Warren W. Green, Jordan C. Moretta, Lian Zhang, Robert J. Campbell, Jeffrey R. Martens
Summary: Olfactory sensory neurons (OSNs) mature by developing glomeruli with multiple cilia, and a GTPase called ARL13B plays a crucial role in this maturation process. Loss of ARL13B in immature OSNs causes dysregulation of cellular homeostasis and delays the timing of maturation. Additionally, ARL13B is essential for the proper structure and innervation of glomeruli, contributing to odor detection and perception.
