The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by est...The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by establishing membrane contact sites(MCSs).These contacts regulate organelle positioning and remodeling,including fusion and fission,facilitate precise lipid exchange,and couple vital signaling events.Here,we systematically review recent advances and converging themes on ER-involved organellar contact.The molecular basis,cellular influence,and potential physiological functions for ER/nuclear envelope contacts with mitochondria,Golgi,endosomes,lysosomes,lipid droplets,autophagosomes,and plasma membrane are summarized.展开更多
Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understandi...Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific pathology.Astrocytes,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including AD.Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways.Tumor-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in AD.Surprisingly,no stable cell lines were available from genetic mouse AD models.Recently,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary cultures.Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier models.Here we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived astrocytes.We conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.展开更多
真核生物细胞中,双层膜细胞器线粒体会进行持续的分裂与融合,从而改变自身形态来满足细胞在不同生长条件下的能量代谢需求.除此之外,线粒体的动态与功能还依赖于与其他细胞器的互作及一些代谢产物在互作过程中的双向交流.与线粒体互作...真核生物细胞中,双层膜细胞器线粒体会进行持续的分裂与融合,从而改变自身形态来满足细胞在不同生长条件下的能量代谢需求.除此之外,线粒体的动态与功能还依赖于与其他细胞器的互作及一些代谢产物在互作过程中的双向交流.与线粒体互作的细胞器包括脂滴、过氧化物酶体、液泡和内质网等.在真菌细胞中,线粒体与内质网的互作由存在二者之间的内质网-线粒体接触复合物(ER and mitochondria encounter structure,ERMES)介导.ERMES复合物对于维持线粒体的形态和功能至关重要,其破坏会影响线粒体的动态、钙离子信号、磷脂组分的转运、真菌耐药性和致病真菌的毒力等.本文着重对ERMES复合物在真菌细胞中的组装、功能及其组装调控机制进行系统的总结和讨论.展开更多
In the goat oviductal isthmus,the ICC showed spindle shaped bipolar morphologies with a large nuclear to cytoplasmic content ratio,numerous mitochondria,rough endoplasmic reticulum and many caveolae.They were frequent...In the goat oviductal isthmus,the ICC showed spindle shaped bipolar morphologies with a large nuclear to cytoplasmic content ratio,numerous mitochondria,rough endoplasmic reticulum and many caveolae.They were frequently found near the nerve fibers and the blood vessels.No specialized contacts could be observed between the ICC and the muscles or nerves,except the labyrinthic展开更多
基金supported by the National Natural Science Foundation of China(92254305)supported by the National Natural Science Foundation of China(92254305,91854204,32130026)+20 种基金supported by National Natural Science Foundation of China(92254302,32225013,32130023)supported by the National Natural Science Foundation of China(91954201,31971289)supported by grants from the National Natural Science Foundation of China(91954207)supported by the National Natural Science Foundation of China(32170753)supported by the National Natural Science Foundation of China(32170692,92154001)supported by grants from the National Natural Science Foundation of China(92254303,32170701)supported by grants from the National Natural Science Foundation of China(32101000,32271273)the Strategic Priority Research Program(XDB39000000)Project for Young Scientists in Basic Research(YSBR-075)of the Chinese Academy of Sciencesthe National Key Research and Development Program of China(2021YFA1300800)National Key Research and Development Program of China(2021YFA0804802,2019YFA0508602)Beijing Natural Science Foundation(JQ20028)New Cornerstone Science Foundation(Xplorer Prize)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB37020304)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB37040402)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA24030205)the National Key Research and Development Program of China(2021YFA1300301)the National Key Research and Development Program of China(2018YFA0506902)the Fundamental Research Funds for the Central Universities(63213104,63223043)the Talent Training Project at Nankai University(035-BB042112)supported by the Beijing Municipal Science&Technology Commission(5202022)。
文摘The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by establishing membrane contact sites(MCSs).These contacts regulate organelle positioning and remodeling,including fusion and fission,facilitate precise lipid exchange,and couple vital signaling events.Here,we systematically review recent advances and converging themes on ER-involved organellar contact.The molecular basis,cellular influence,and potential physiological functions for ER/nuclear envelope contacts with mitochondria,Golgi,endosomes,lysosomes,lipid droplets,autophagosomes,and plasma membrane are summarized.
基金supported by fellowship to a grant from CRT Foundation,No.1393-2017(to LT)grants from the Fondazione Cariplo,Nos.2013-0795(to AAG),2014-1094(to DL)grants from The Universitàdel Piemonte Orientale,Nos.FAR-2016(to DL),FAR-2019(to DL)。
文摘Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific pathology.Astrocytes,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including AD.Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways.Tumor-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in AD.Surprisingly,no stable cell lines were available from genetic mouse AD models.Recently,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary cultures.Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier models.Here we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived astrocytes.We conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.
文摘真核生物细胞中,双层膜细胞器线粒体会进行持续的分裂与融合,从而改变自身形态来满足细胞在不同生长条件下的能量代谢需求.除此之外,线粒体的动态与功能还依赖于与其他细胞器的互作及一些代谢产物在互作过程中的双向交流.与线粒体互作的细胞器包括脂滴、过氧化物酶体、液泡和内质网等.在真菌细胞中,线粒体与内质网的互作由存在二者之间的内质网-线粒体接触复合物(ER and mitochondria encounter structure,ERMES)介导.ERMES复合物对于维持线粒体的形态和功能至关重要,其破坏会影响线粒体的动态、钙离子信号、磷脂组分的转运、真菌耐药性和致病真菌的毒力等.本文着重对ERMES复合物在真菌细胞中的组装、功能及其组装调控机制进行系统的总结和讨论.
基金supported by the National Natural Science Foundation of China(31570246 and 32170279)the Fundamental Research Funds for the Central Universities(2572019CT03)。
文摘In the goat oviductal isthmus,the ICC showed spindle shaped bipolar morphologies with a large nuclear to cytoplasmic content ratio,numerous mitochondria,rough endoplasmic reticulum and many caveolae.They were frequently found near the nerve fibers and the blood vessels.No specialized contacts could be observed between the ICC and the muscles or nerves,except the labyrinthic
