DTD1 modulates synaptic efficacy by maintaining D-serine and D-aspartate homeostasis  

作　　者：Xiao Liu Chaojuan Yang Zhuoran Lin Jianing Li Bin Yin Xuepei Lei Wei Han Boqin Qiang Pengcheng Shu Chen Zhang Xiaozhong Peng 

机构地区：[1]State KeyLaboratoryofCommon Mechanism Research for Major Diseases,Departmentof Biochemistry&Molecular Biology,MedicalPrimate Research Center,NeuroscienceCenter,Instituteof Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing 100005,China [2]State Key Laboratory of Respiratory Health and Multimorbidity,Beijing 100005,China [3]Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100021,China [4]School of Basic Medical Sciences,Beijing Key Laboratory of Neural Regeneration and Repair,Capital Medical University,Beijing 100069,China [5]Key Laboratoryof Biomechanics and Mechanobiology(Beihang University),Ministryof Education,Beijing AdvancedInnovation Center for Biomedical Engineering,Schoolof Engineering Medicine,Beihang University,Beijing 100191,China [6]Chinese Institute for Brain Research,Beijing 102206,China

出　　处：《Science China(Life Sciences)》2025年第2期467-483,共17页中国科学(生命科学英文版)

基　　金：supported by the National Science and Technology Innovation 2030 Grants of China(2021ZD0200902 to Peng,X.);the National Key Research and Development Program of China(2017YFA0105201 to Zhang,C.);the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS;2021-1-I2M-019 to Shu,P.and 2021-1-I2M-024 to Peng,X.);the National Natural Science Foundation of China(31670789 to Peng,X.,32370883 to Shu,P.,81925011 to Zhang,C.,82001145 to Yang,C.);the State Key Laboratory Special Fund 2060204。

摘　　要：D-serine and D-aspartate are involved in N-methyl-D-aspartate receptor(NMDAR)-related physiological and pathological processes.Daminoacyl-t RNA deacylase 1(DTD1)may biochemically contribute to D-serine or D-aspartate production.However,it is unclear thus far whether DTD1 regulates D-serine or D-aspartate content in neurobiological processes.In the present research,we found that DTD1 was essential to maintain the D-serine or D-aspartate homeostasis,which was consistent with the phenomenon that DTD1-deficiency resulted in changes in the quantity changes of functional NMDAR subunits in postsynaptic compartments.Moreover,DTD1 played a considerable role in regulating dendritic morphology and synaptic structure.As a consequence,DTD1 affected neurobiological events,including the synaptic strength of the CA3-to-CA1 circuit,dendritic spine density of hippocampal pyramidal neurons,and behavioral performance of mice in the Morris water maze.These findings highlight the important role of DTD1 in synaptic transmission,neuronal morphology,and spatial learning and memory and suggest an undisclosed mechanism of DTD1 that participates the regulation of D-serine or D-aspartate homeostasis in hippocampal neurons.

关 键 词：D-aminoacyl-tRNA deacylase 1 D-SERINE D-ASPARTATE synaptic transmission neuronal morphology spatial learning and memory 

分 类 号：R338[医药卫生—人体生理学]