Phosphoinositides （Pls） have long been known to have an essential role in cell physiology. Their intracellular localization and concentration must be tightly regulated for their proper function. This spatial and tem...Phosphoinositides （Pls） have long been known to have an essential role in cell physiology. Their intracellular localization and concentration must be tightly regulated for their proper function. This spatial and temporal regulation is achieved by a large number of PI kinases and phosphatases that are present throughout eukaryotic species. One family of these enzymes contains a conserved PI phosphatase domain termed Sac. Although the Sac domain is homologous among different Sac domain-containing proteins, all appear to exhibit varied substrate specificity and subcellular localization. Dysfunctions in several members of this family are implicated in a range of human diseases such as cardiac hypertrophy, bipolar disorder, Down＇s syndrome, Charcot-Marie-Tooth disease （CMT） and Amyotrophic Lateral Sclerosis （ALS）. In plant, several Sac domain-containing proteins have been implicated in the stress response, chloroplast function and polarized secretion. In this review, we focus on recent findings in the family of Sac domain-containing PI phosphatases in yeast, mammal and plant, including the structural analysis into the mechanism of enzymatic activity, cellular functions, and their roles in disease pathophysiology.展开更多
Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum(ER)membrane.It is ubiquitously expressed and functions as a cargo receptor,mediating cargo transport from the ER to th...Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum(ER)membrane.It is ubiquitously expressed and functions as a cargo receptor,mediating cargo transport from the ER to the Golgi apparatus via the canonical coat protein complex Il(CoPll)-coated vesicles or specific vesicles.It also participates in ER-Golgi protein trafficking through a tubular network.Meanwhile,it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through Coplcoated vesicles.Surf4 can selectively mediate export of diverse cargos,such as PCSK9 very low-density lipoprotein(VLDL),progranulin,α1-antitrypsin,STING,proinsulin,and erythropoietin.It has been implicated in facilitating VLDL secretion,promoting cell proliferation and migration,and increasing replication of positive-strand RNA viruses.Therefore,Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target.However,the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER-Golgi protein trafficking remain elusive.Here,we summarize the most recent advances in Surf4,focusing on its role in lipid metabolism.展开更多
The stability of cnidarian-dinoflagellate endosymbioses is dependent upon communication between the host gastrodermal cell and the symbionts housed within it. Although the molecular mechanisms remain to be elucidated,...The stability of cnidarian-dinoflagellate endosymbioses is dependent upon communication between the host gastrodermal cell and the symbionts housed within it. Although the molecular mechanisms remain to be elucidated, existing evidence suggests that the establishment of these endosymbioses may involve the sorting of membrane proteins. The present study examined the role of host gastrodermal membranes in regulating symbiont （genus Symbiodinium） photosynthesis in the stony coral Euphyllia glabrescens. In comparison with the photosynthetic behavior of Symbiodinium in culture, the Symbiodinium populations within isolated symbiotic gastrodermal cells （SGCs） exhibited a significant degree of photo-inhibition, as determined by a decrease in the photochemical efficiency of photosystem II （Fv/Fm）. This photo-inhibition coincided with increases in plasma membrane perturbation and oxidative activity in the SGCs. Membrane trafficking in SGCs was examined using the metabolism of a fluo- rescent lipid analog, N-[5-（5,7-dimethyl boron dipyrromethene difluoride）-l-pentanoyl]-D-erythro-Sphingosylpbosphoryl- choline （BODIPY-Sphingomyelin or BODIPY-SM）. Light irradiation altered both membrane distribution and trafficking of BODIPY-SM, resulting in metabolic changes. Cholesterol depletion of the SGC plasma membranes by methyl-13-cyclodextrin retarded BODIPY-SM degradation and further augmented Symbiodinium photo-inhibition. These results indicate that Symbio- dinium photo-inhibition may be related to perturbation of the host gastrodermal membrane, providing evidence for the pivotal role of host membrane trafficking in the regulation of this environmentally important coral-dinoflagellate endosymbiosis.展开更多
文摘Phosphoinositides （Pls） have long been known to have an essential role in cell physiology. Their intracellular localization and concentration must be tightly regulated for their proper function. This spatial and temporal regulation is achieved by a large number of PI kinases and phosphatases that are present throughout eukaryotic species. One family of these enzymes contains a conserved PI phosphatase domain termed Sac. Although the Sac domain is homologous among different Sac domain-containing proteins, all appear to exhibit varied substrate specificity and subcellular localization. Dysfunctions in several members of this family are implicated in a range of human diseases such as cardiac hypertrophy, bipolar disorder, Down＇s syndrome, Charcot-Marie-Tooth disease （CMT） and Amyotrophic Lateral Sclerosis （ALS）. In plant, several Sac domain-containing proteins have been implicated in the stress response, chloroplast function and polarized secretion. In this review, we focus on recent findings in the family of Sac domain-containing PI phosphatases in yeast, mammal and plant, including the structural analysis into the mechanism of enzymatic activity, cellular functions, and their roles in disease pathophysiology.
基金This work was supported by grants from Canadian Institutes of Health Research(PS 178091)the National Natural Science Foundation of China(NSFC 81929002)+3 种基金D.-W.Z.was also supported by grants from the Natural Sciences and Engineering Research Council of Canada(RGPIN-2016-06479)Canadian Institutes of Health Research(PS 155994)S.Q.was supported by 91539114,ts201511057,and Academic Promotion Program of Shandong First Medical University(2019QL010 and 2019PT009)Y.S.was partly supported by Motyl Graduate Studentships in Cardiac Sciences from the Faculty of Medicine and Dentistry at the University of Alberta.
文摘Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum(ER)membrane.It is ubiquitously expressed and functions as a cargo receptor,mediating cargo transport from the ER to the Golgi apparatus via the canonical coat protein complex Il(CoPll)-coated vesicles or specific vesicles.It also participates in ER-Golgi protein trafficking through a tubular network.Meanwhile,it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through Coplcoated vesicles.Surf4 can selectively mediate export of diverse cargos,such as PCSK9 very low-density lipoprotein(VLDL),progranulin,α1-antitrypsin,STING,proinsulin,and erythropoietin.It has been implicated in facilitating VLDL secretion,promoting cell proliferation and migration,and increasing replication of positive-strand RNA viruses.Therefore,Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target.However,the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER-Golgi protein trafficking remain elusive.Here,we summarize the most recent advances in Surf4,focusing on its role in lipid metabolism.
基金The present study is dedicated to the memory of our mentor Professor Richard E.Pagano (1944 2010)supported by the National Science Council of Taiwan (Grant No.NSC 98-2311-B-291-001-MY3).
文摘The stability of cnidarian-dinoflagellate endosymbioses is dependent upon communication between the host gastrodermal cell and the symbionts housed within it. Although the molecular mechanisms remain to be elucidated, existing evidence suggests that the establishment of these endosymbioses may involve the sorting of membrane proteins. The present study examined the role of host gastrodermal membranes in regulating symbiont （genus Symbiodinium） photosynthesis in the stony coral Euphyllia glabrescens. In comparison with the photosynthetic behavior of Symbiodinium in culture, the Symbiodinium populations within isolated symbiotic gastrodermal cells （SGCs） exhibited a significant degree of photo-inhibition, as determined by a decrease in the photochemical efficiency of photosystem II （Fv/Fm）. This photo-inhibition coincided with increases in plasma membrane perturbation and oxidative activity in the SGCs. Membrane trafficking in SGCs was examined using the metabolism of a fluo- rescent lipid analog, N-[5-（5,7-dimethyl boron dipyrromethene difluoride）-l-pentanoyl]-D-erythro-Sphingosylpbosphoryl- choline （BODIPY-Sphingomyelin or BODIPY-SM）. Light irradiation altered both membrane distribution and trafficking of BODIPY-SM, resulting in metabolic changes. Cholesterol depletion of the SGC plasma membranes by methyl-13-cyclodextrin retarded BODIPY-SM degradation and further augmented Symbiodinium photo-inhibition. These results indicate that Symbio- dinium photo-inhibition may be related to perturbation of the host gastrodermal membrane, providing evidence for the pivotal role of host membrane trafficking in the regulation of this environmentally important coral-dinoflagellate endosymbiosis.
