Article
Cell Biology
Heather Tsong, Erika L. F. Holzbaur, Andrea K. H. Stavoe
Summary: Misregulation of neuronal autophagy is involved in age-related neurodegenerative diseases. Aging leads to a decrease in autophagosome formation rate and density along the axon, but an increase in autophagic vesicle maturation. Late aging results in a significant loss of acidified vesicles in the distal axon, while the efficient transport of autophagic vesicles in both proximal and distal axons is maintained during early aging. These findings suggest that aging differentially impacts distinct aspects of neuronal autophagy.
Article
Biology
Mengjing Bao, Ruth E. Doerig, Paula Maria Vazquez-Pianzola, Dirk Beuchle, Beat Suter
Summary: In this study, the glutamylation of a-tubulin isotypes in Drosophila ovaries was investigated. It was found that the C-terminal ends of alpha Tub84B/D were glutamylated, while alpha Tub67C was not. TTLL5 was identified as the protein responsible for mono- and poly-glutamylation of alpha Tub84B/D and its proper localization. This study also demonstrated the dependence of kinesin-1 distribution, as well as other cellular functions such as axonal transport and ooplasmic streaming, on TTLL5 and alpha-tubulin glutamylation.
Article
Biochemistry & Molecular Biology
Francesca Mattedi, Ethlyn Lloyd-Morris, Frank Hirth, Alessio Vagnoni
Summary: Miro GTPases control mitochondrial morphology, calcium homeostasis, and regulate mitochondrial distribution. However, the spatial and temporal integration of Miro proteins' functions is not clear yet. The researchers have developed an optogenetic loss of function Split-Miro allele to investigate this issue. They found that rapid optogenetic cleavage of Split-Miro leads to rearrangement of the mitochondrial network, but it does not affect calcium buffering or association with the endoplasmic reticulum. Overexpression of Split-Miro increases mitochondrial motility, but sustained photocleavage shows that it is not essential for maintaining elevated mitochondrial processivity. In vivo experiments show that Split-Miro photocleavage affects mitochondrial trafficking and neuronal activity, highlighting its important role in regulating locomotor activity.
Article
Cell Biology
Thomas J. Krzystek, Joseph A. White, Rasika Rathnayake, Layne Thurston, Hayley Hoffmar-Glennon, Yichen Li, Shermali Gunawardena
Summary: This study reveals a novel role for HTT in the retrograde movement of a Rab7-LAMP1-containing signaling late endosome and identifies adaptors Hip1 and Rilpl as important factors in this process.
Review
Neurosciences
Padmashri Naren, Khan Sabiya Samim, Kamatham Pushpa Tryphena, Lalitkumar K. Vora, Saurabh Srivastava, Shashi Bala Singh, Dharmendra Kumar Khatri
Summary: The inter-neuronal communication in neuronal cells is achieved through the microtubule-mediated axonal transport system. Modifying microtubule stability can enhance efficient axonal transport and this has important implications for the treatment of neurodegenerative diseases.
TRANSLATIONAL NEURODEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Yukinobu Mizuhara, Mitsunori Takano
Summary: Through molecular dynamics simulations, it was observed that KIF1A exhibits biased Brownian motion along MT as it binds to MT, with the bias toward the plus-end generated by a ratchet-like energy landscape for the KIF1A-MT interaction involving electrostatic interaction and the negatively-charged C-terminal tail (CTT) of tubulin. The relevance to post-translational modifications of CTT is also discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Amrita Mandal, Hiu-Tung C. Wong, Katherine Pinter, Natalie Mosqueda, Alisha Beirl, Richa Madan Lomash, Sehoon Won, Katie S. Kindt, Catherine M. Drerup
Summary: Research shows that retrograde mitochondrial transport plays a crucial role in maintaining the homeostatic distribution of mitochondria in neurons, and disrupting this process can lead to accumulation of aged organelles in axon terminals and loss of mitochondria in the cell body.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biology
Victoria L. Hewitt, Leonor Miller-Fleming, Madeleine J. Twyning, Simonetta Andreazza, Francesca Mattedi, Julien Prudent, Franck Polleux, Alessio Vagnoni, Alexander J. Whitworth
Summary: The protein Pdzd8 plays a critical role in the regulation of mitochondrial quality control and neuronal homeostasis. Decreasing Pdzd8-mediated mitochondria-endoplasmic reticulum contact sites (MERCs) can slow age-associated decline in locomotor activity and increase lifespan in Drosophila. On the other hand, increasing MERCs disrupts mitochondria transport and synapse formation, accelerates age-related decline in locomotion, and reduces lifespan. Additionally, reducing Pdzd8 protein can rescue locomotor defects in a fly model of Alzheimer's disease.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Pamela Meneses Iack, Danielle Rayee, Roberto Lent, Victor Tulio Ribeiro-Resende, Patricia P. Garcez
Summary: Cenpj is a gene that regulates axon growth and plays an important role in cortical development. This study found that silencing Cenpj in a mouse model leads to increased axonal length, more branches, larger growth cone area, and more stable microtubules. These findings suggest that Cenpj could be a novel target for axonal regeneration.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Saravanan Gunaseelan, Ziyin Wang, Venetia Kok Jing Tong, Sylvester Wong Shu Ming, Rafhanah Banu Bte Abdul Razar, Sumitra Srimasorn, Wei-Yi Ong, Kah-Leong Lim, John Jia En Chua
Summary: FEZ1-mediated axonal transport is crucial in central nervous system development, and its deletion may lead to motor impairments. Studies show that FEZ1 is selectively expressed in the brain and spinal cord, and its deletion impairs axon and dendrite development. Pharmacological activation of UNC-51/ATG1 can ameliorate these abnormalities.
HUMAN MOLECULAR GENETICS
(2021)
Article
Multidisciplinary Sciences
Adam R. Fenton, Thomas A. Jongens, Erika L. F. Holzbaur
Summary: Mitochondria are transported along microtubules by opposing kinesin and dynein motors, linked by TRAK adaptor proteins. TRAK2 activates kinesin-1 for transport toward the plus-end of microtubules and acts as a dynein activating adaptor for transport toward the minus-end. At a sufficient level, the dynein-binding protein LIS1 is necessary for efficient dynein-mediated TRAK2 transport. TRAK2 forms a complex containing both kinesin-1 and dynein-dynactin, functionally linking these motors and coordinating their activities for proper mitochondrial transport.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Ana Catarina Costa, Monica Mendes Sousa
Summary: Neurons are polarized cells and the regulation of the microtubule cytoskeleton is crucial for their function. A group of microtubule-severing enzymes, including spastin, have been found to play an important role in regulating microtubule organization and axonal transport.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Editorial Material
Cell Biology
Angelika B. Harbauer, Thomas L. Schwarz
Summary: In this study, the authors found that axonal mitophagy relies on local translation of Pink1 mRNA. The co-transport of Pink1 mRNA with mitochondria in neurons plays a crucial role in mitophagy in the distal parts of the cell. This finding contributes to our understanding of mitochondrial homeostasis in neurons.
Article
Neurosciences
Caleb A. Doll, Kayt Scott, Bruce Appel
Summary: Research has found that Fmrp regulates cell specification in pMN progenitor cells, leading to fewer motor neurons and excess OPCs in fmr1 mutant zebrafish, while also promoting the differentiation of OPCs. The results suggest that Fmrp has cell stage-specific requirements for the specification and differentiation of oligodendrocyte lineage cells.
Article
Cell Biology
Di Ma, Binbin Deng, Chao Sun, David W. McComb, Chen Gu
Summary: This study investigates the formation mechanism of axonal varicosities using confocal microscopy and cryo-electron tomography. The results reveal that non-uniform mechanical interactions can lead to significant diameter variation in axons, and bundling axons reduces the level of varicosities.
Letter
Cell Biology
Lei Gu, Longfei Wang, Hao Chen, Jiaxu Hong, Zhangfei Shen, Abhinav Dhall, Taotao Lao, Chaozhong Liu, Zheng Wang, Yifan Xu, Hong-Wen Tang, Damayanti Chakraborty, Jiekai Chen, Zhihua Liu, Dragana Rogulja, Norbert Perrimon, Hao Wu, Yang Shi
Article
Cell Biology
Elsayed Metwally, Guoli Zhao, Qifu Wang, Yong Q. Zhang
Summary: The study reveals that Ttm50 modulates calpain activity and localization by interacting with calpain, increasing calpain's calcium sensitivity, shedding new light on calpain-associated pathologies.
Article
Biochemical Research Methods
Xuehua Ma, Zhiguang Zhao, Long Xiao, Weina Xu, Yahui Kou, Yanping Zhang, Gang Wu, Yangyang Wang, Zhuo Du
Summary: This study utilizes a protein expression atlas to uncover cell fate and regulatory factors in Caenorhabditis elegans embryonic development. The research reveals the spatiotemporal expression patterns of TFs and a series of TFs that specify developmental states. Furthermore, the atlas uncovers the unexpected role of unknown TFs in neurogenesis and muscle differentiation.
Review
Neurosciences
Elsayed Metwally, Guoli Zhao, Yong Q. Zhang
Summary: Calpains are Ca2+-activated cysteine proteases that act at neutral pH, with tightly regulated activity. Genetic mutations in calpain genes are associated with human diseases, and elevated Ca2+ levels can promote calpain activation in pathologies.
TRENDS IN NEUROSCIENCES
(2021)
Correction
Biochemical Research Methods
Xuehua Ma, Zhiguang Zhao, Long Xiao, Weina Xu, Yahui Kou, Yanping Zhang, Gang Wu, Yangyang Wang, Zhuo Du
Article
Biology
Hui Zhao, Jianping Zhao, Di Wu, Zhaolin Sun, Yang Hua, Min Zheng, Yumei Liu, Qi Yang, Xiahe Huang, Yuan Li, Yueshan Piao, Yingchun Wang, Sin Man Lam, Huijuan Xu, Guanghou Shui, Yongjun Wang, Haifeng Yao, Liangxue Lai, Zhuo Du, Jidong Mi, Enqi Liu, Xunming Ji, Yong Q. Zhang
Summary: This study demonstrates the generation of ApoE knockout dogs using CRISPR/Cas9 and somatic cell nuclear transfer technologies, which exhibit hypercholesterolemia and severe atherosclerosis with clinical manifestations. The characteristics of hypercholesterolemia and atherosclerosis in mutant dogs and their offspring make them valuable models for developing and evaluating new therapies against atherosclerosis and related disorders, as they closely resemble human patients more than other animal models.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Biochemical Research Methods
Huilin Hong, Zhiguang Zhao, Xiahe Huang, Chao Guo, Hui Zhao, Guo-Dong Wang, Ya-Ping Zhang, Jian-Ping Zhao, Jianhui Shi, Qing-Feng Wu, Yong-Hui Jiang, Yingchun Wang, Lei M. Li, Zhuo Du, Yong Q. Zhang, Ying Xiong
Summary: This study analyzed proteomes from six regions of the postnatal brain at three developmental stages of domestic dogs, revealing the correlation between myelination and hippocampus-related proteins in dogs and humans. The global expression patterns of disease-associated proteins in the brain of dogs resemble those in humans more than in mice. These findings provide insights into brain development and function, and can guide mechanistic and translational research using appropriate animal models.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Review
Biochemistry & Molecular Biology
Hui Zhao, Enqi Liu, Yong Q. Zhang
Summary: Cardiovascular diseases (CVD) are a major cause of death worldwide, and dog models can be useful in studying the mechanisms of atherosclerosis and developing new treatment strategies.
Article
Genetics & Heredity
Ting Zhao, Liying Guan, Xuehua Ma, Baohui Chen, Mei Ding, Wei Zou
Summary: In this study, it was found that knock-out of C. elegans gene chdp-1 leads to deficits in dendrite formation during the larval stages and spontaneous dendrite degeneration in adulthood. The assembly of actin in dendritic growth cones is significantly reduced in the chdp-1 mutants. Loss of chdp-1 also affects the assembly of microtubule cytoskeleton, intracellular organelle transport, and neuropeptide secretion. Knock-out of sax-1 suppresses the defects mentioned above in chdp-1 mutants.
Letter
Biochemistry & Molecular Biology
Huijuan Xu, Haiyang Hao, Shirui Wang, Xueru Liu, Wen Lyu, Zhentao Zuo, Yan Zhuo, Jidong Mi, Yong Q. Zhang, Rui Tian, Huijuan Zhu
JOURNAL OF GENETICS AND GENOMICS
(2023)
Review
Biochemistry & Molecular Biology
Ying Xiong, Huilin Hong, Cirong Liu, Yong Q. Zhang
Summary: This article presents a systematic review on the brain changes induced by social isolation at different ages and in different animal models. The findings suggest that social isolation can lead to social and cognitive deficits, as well as an increased occurrence of depression and anxiety. Abnormal neurotransmission, neural circuitry, and glial cell development and function may contribute to these emotional and behavioral abnormalities. The authors propose the use of alternative animal models with brain structures and complex social behaviors similar to humans to bridge the gap between animal and human studies on social isolation.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Xiaoxiao Niu, Chuan-Xi Mao, Shan Wang, Xiongxiong Wang, Youyu Zhang, Juncheng Hu, Ran Bi, Zhihua Liu, Jin Shan
Summary: The posttranslational modification of tubulin, specifically acetylation of alpha-tubulin, is essential for the dynamic complexity and functional diversity of microtubules. Knocking out the alpha-tubulin acetyltransferase gene and mutating the acetylation site have been shown to impair dendritic development and locomotion in larval neurons. These findings contribute to our understanding of the role of alpha-tubulin acetylation in neuronal development and function.
Article
Cell Biology
Md Shafayat Hossain, Aiyu Yao, Xinhua Qiao, Wenwen Shi, Ting Xie, Chang Chen, Yong Q. Zhang
Summary: Glutathionylation is a vital posttranslational modification involved in nervous system development, regulating synapse growth through the degradation of Gbb. This study uncovers the crosstalk between glutathionylation and ubiquitination, providing new insights into their interplay.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wei Ren, Kang Huang, Yumo Li, Qin Yang, Liping Wang, Kun Guo, Pengfei Wei, Yong Q. Zhang
Summary: This study developed a pupilometer for dogs and used it to measure real-time pupillary responses. The researchers found that gene-edited dogs carrying mutations in Shank3 showed altered pupillary responses to light, loud noise, and high reward food. The Shank3 mutant dogs also exhibited impaired pupillary synchrony during dog-human interaction. These findings suggest that the pupilometer can be used to study the underlying neural mechanisms of autism spectrum disorder and other psychiatric disorders.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Shengquan Zhang, Xiongxiong Wang, Zhihua Liu, Shan Jin, Chuan-Xi Mao
Summary: The microtubule network plays a crucial role in the nervous system and is associated with various neurodevelopmental disorders and neurological diseases. This study introduces a method for visualizing microtubule networks in Drosophila melanogaster and reveals the regulatory role of Katanin 60 in neurodevelopment. The protocol provides a valuable tool for genetic screening and microtubule dynamics analysis in the nervous system.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)