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Journal of Molecular Cell Biology 2021年第5期13卷 392-394页

作者： Yuqian Shen junhai han Zi Chao Zhang School of Life Science and Technology Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226001China

Protein synthesis involves initiation,elongation,and termination.A number of studies show that translation elongation is highly regulated and is the most energy-intensive process,which controls the efficiency and accuracy of protein *** the elongation process,eukaryotic elongation factor 2(eEF2)binds to the ribosome to induce its conformation change and promotes the translocation of the tRNAs by hydrolyzing guanosine triphosphate,which then allows the next AA-tRNA to enter the A site for translation *** activity of eEF2 is negatively regulated by its kinase eEF2K that phosphorylates eEF2 at threonine-56(Thr56).

关键词： synthesis EF2 translational

Drosophila Studies on Autism Spectrum Disorders

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Neuroscience Bulletin 2017年第6期33卷 737-746页

作者： Yao Tian Zi Chao Zhang junhai han Institute of Life Sciences The Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China

In the past decade, numerous genes associated with autism spectrum disorders（ASDs） have been identified. These genes encode key regulators of synaptogenesis,synaptic function, and synaptic plasticity. Drosophila is a prominent model system for ASD studies to define novel genes linked to ASDs and decipher their molecular roles in synaptogenesis, synaptic function, synaptic plasticity, and neural circuit assembly and consolidation. Here, we review Drosophila studies on ASD genes that regulate synaptogenesis, synaptic function, and synaptic plasticity through modulating chromatin remodeling, transcription, protein synthesis and degradation, cytoskeleton dynamics, and synaptic scaffolding.

关键词： Autism spectrum disorders Drosophila Chromatin remodeling Synaptic scaffolding Synaptic transmission

The First National Prevalence of Autism Spectrum Disorder in China

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Neuroscience Bulletin 2020年第9期36卷 959-960页

作者： Zi Chao Zhang junhai han School of Life Science and Technology Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China

Autism spectrum disorder (ASD) is a complex developmental disability characterized by impaired social interaction and communication,restricted interests,and stereotypical behaviors [1,2].In addition to these core diagnostic features,children with ASD frequently present with a host of associated behavioral issues,such as intellectual disability and epilepsy,as well as feeding and sleep *** prevalence of ASD in the United States is about 1/59,with a significantly higher proportion in males [3].Therefore,ASD is no longer a rare disorder.

关键词： impaired epilepsy restricted

Bidirectional regulation of fragile X mental retardation protein phosphorylation controls rhodopsin hornoeostasis

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Journal of Molecular Cell Biology 2017年第2期9卷 104-116页

作者： Xiao Wang Yawen Mu Mengshi Sun junhai han Institute of Life Sciences The Key Laboratory of Developmental Genes and Human Disease Southeast University Nanjing 210096 China Co-innovation Center of Neuroregeneration Nantong University Nantong 226001 China

Homoeostatic regulation of the light sensor, rhodopsin, is critical for the maintenance of light sensitivity and survival of photore- ceptors. The major fly rhodopsin, Rhl, undergoes light-induced endocytosis and degradation, but its protein and mRNA levels remain constant during light/dark cycles. It is not clear how translation of Rhl is regulated. Here, we show that adult photorecep- tors maintain a constant, abundant quantity of ninaE mRNA, which encodes Rhl. We demonstrate that the Fmrl protein associ- ates with ninaE mRNA and represses its translation. Further, light exposure triggers a calcium-dependent dephosphorylation of Fmrl, which relieves suppression of Rhl translation. We demonstrate that Mts, the catalytic subunit of protein phosphatase 2A （PP2A）, mediates light-induced Fmrl dephosphorylation in a regulatory B subunit of PP2A （CKa）-dependent manner. Finally, we show that blocking light-induced Rhl translation results in reduced light sensitivity. Our results reveal the molecular mechanism of Rhl homoeostasis and physiological consequence of Rhl dysregulation.

关键词： G protein-coupled receptor rhodopsin fragile X mental retardation protein dephosphorylation calcium protein phosphatase 2A

Phototransduction in Drosophila

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Science China(Life Sciences) 2012年第1期55卷 27-34页

作者： TIAN Yao HU Wen TONG HuaWei han junhai Institute of Life Science the Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China

The Drosophila visual transduction is the fastest known G protein-coupled signaling cascade and has been served as a model for understanding the molecular mechanisms of other G protein-coupled signaling cascades. Numbers of components in visual transduction machinery have been identified. Based on the functional characterization of these genes, a model for Drosophila phototransduction has been outlined, including rhodopsin activation, phosphoinoside signaling, and the opening of TRP and TRPL channels. Recently, the characterization of mutants, showing slow termination, revealed the physiological significance and the mechanism of rapid termination of light response.

关键词： GPCR signaling visual transduction rhodopsin TRP channels Drosophila

Proteolytic cleavage is required for functional neuroligin 2 maturation and trafficking in Drosophila

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Journal of Molecular Cell Biology 2017年第3期9卷 231-242页

作者： Renjun Tu Jinjun Qian Menglong Rui Nana Tao Mingkuan Sun Yan Zhuang Huihui Lv junhai han Moyi Li Wei Xie Institute of Life Sciences The Collaborative Innovation Center for Brain Science Southeast University 2 SiPaiLou Road Nanjin8 210096 China The Key Laboratory of Developmental Genes and Human Disease Jiangsu Co-innovation Center of Neuroregeneration Southeast University2 SiPaiLou Road Nanjing 210096 China

Neuroligins （Nlgs） are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroUgin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Nlgs are mostly retained in the endoplasmic reticulum （ER）. However, the mechanisms underlying normal Nlg maturation and trafficking have remained largely unknown. Here, we found that Drosophila neuroligin 2 （DNlg2） undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages. A region encompassing Y642-T698 is required for this process. The immature non-cleavable DNtg2 is retained in the ER and non-functionaL The C-terminal fragment of DNlg2 instead of the full-length or non-cleavable DNIg2 is able to rescue neuromuscular junction defects and GluRIIB reduction induced by dnlg2 deletion. Intriguingly, the autism-associated R598C mutation in DNIg2 leads to similar marked defects in DNIg2 proteo- lytic process and ER export, revealing a potential role of the improper Nlg cleavage in autism pathogenesis. Collectively, our find- ings uncover a specific mechanism that controls DNIg2 maturation and trafficking via proteolytic cleavage in the ER, suggesting that the perturbed proteolytic cleavage of Nlgs likely contributes to autism disorder.

关键词： neuroligin proteolytic cleavage maturation trafficking autism

Feedback regulation in Drosophila visual circuits

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Feedback regulation in Drosophila visual circuits

中国神经科学学会第十届全国学术会议

作者： Wen Hu junhai han Institute of Life Sciences Southeast University

High temporal resolution of vision relies on the rapid kinetics of the photoresponse in the light-sensing photoreceptor *** is well known that the activation/deactivation of photoreceptor largely depends on the visual transduction cascades within ***,how photoreceptor neurons achieve the stable resting membrane potential is not *** we showed that Ih channels play an essential role in regulating photoreceptor cell activity through retinal- lamina *** performed an ERG-based mutagenesis screen and isolated a mutant fly which exhibits spontaneous photoreceptor neurons firing in *** spontaneous activation of photoreceptor neuron can be suppressed by either blocking phototransduction cascades or the neurotransmitter release from photoreceptor *** immunostaining,we indentified that Ih channels expressed in LI,L2 lamina neurons and retinal base glia *** studies indicated that the retina-lamina microcircuits are involved in the regulation of photoreceptor activity.

关键词： vision photoreceptor spontaneous activity retina-lamina microcircuit Ih channel

Neurexin regulates night-time sleep through modulating neural excitability

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Neurexin regulates night-time sleep through modulating neura...

2015年中国中西医结合学会时间生物医学专业委员会学术研讨暨换届会议

作者： Huawei Tong Qian Li junhai han Institute of Life Sciences the Key Laboratory of Developmental Genes and Human DiseaseSoutheast University

Sleep is a universal,essential and evolutionarily conserved behavior among animal species,which is regulated by various neural circuits and closely related to synaptic *** are cell adhesion molecules that function in various neural circuits through mediating synapse formation and synaptic ***,the neuronal circuits and the potential role of Neurexins in sleep regulation are not ***,we show that lack of the Drosophila homolog of α-Neurexin significantly reduce night-time sleep and depletion of Neurexin from different kenyon cell populations either increase or decrease night-time *** further identified the role of different KC populations in night-time sleep *** calcium image analysis,we reveal that nrx mutant KCs exhibits an elevated neural excitability,which results in a decreased night-time ***,we demonstrate that Neurexin associates with Na/K-ATPase and promotes its plasma membrane location,which is essential to govern the neural *** study indicate that different KCs populations play variant roles in night-time sleep regulation and Neurexin regulates night-time sleep through modulating the excitability of KCs,which offers the insights into the neural circuit mechanism of sleep regulation and the molecular function of Neurexin.

关键词： Sleep Neural circuit Mushroom body Kenyon cell Neurexin Na+/K+-ATPase neural excitability

A Drosophila metallophosphoesterase mediates deglycosylation of rhodopsin and promotes its transportation and stability in photoreceptor neurons

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A Drosophila metallophosphoesterase mediates deglycosylation...

中国生物化学与分子生物学会第十届会员代表大会暨全国学术会议

作者： Jinguo Cao Yi Li junhai han Southeast University the Key Laboratory of Developmental Genes and Human Disease

Before delivery to the cell surface,the oligosaccharide chains of newly synthesized membrane receptors are trimmed and modified to optimize their trafficking and/or *** the case of Drosophila Rhl rhodopsin,the oligosaccharide chain is entirely removed before it reaches the membrane of rhabdomere,the photosensory organelle in fly photoreceptors. Here we show that a metallophosphoesterase dMPPE functions as a Mn2+/Zn2+-dependent phosphoesterase and mediates Rhl deglycosylation in *** a dmppe mutant,Rhl remained glycosylated and was transported

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PQBP1 mediates neuronal development through regulating cellular adhesion function

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PQBP1 mediates neuronal development through regulating cellu...

第二届全国发育生物学大会

作者： Didi Wan ZiChao Zhang Xiaoyan Zhang junhai han Institute of Life Sciences the Key Laboratory of Developmental Genes and Human DiseaseSoutheast University

Polyglutamine-binding protein 1(PQBP1)has been identified as one of the disease-causing genes for Mental retardation(MR),but its function and pathological mechanism are still largely *** we show that PQBP1 play an essential role in neural development through regulating cellular adhesion in *** mutant flies exhibit severe defects in rhabdomeral morphogenesis as well as in axonal branching of mushroom body *** microscopy studies reveal that the defective rhabdomeral morphogenesis in dPQBPl mutant flies is due to impaired cellular adhesion *** analysis revealed that dPQBP1 is essential for the function of cell adhesion *** data indicate that dPQBP1 regulates neural development through modulating cellular adhesion function and offers insight into the mechanism of POBP1 mutation caused diseases.

关键词： PQBP1 neural development cell adhesion molecule mental retardation