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第十一届全国寄生虫学青年工作者学术研讨会

作者： SHINUO Cao JIAWEN Fu HEMING Chen HONGLIN Jia State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural Sciences

Toxoplasma gondii is an obligate intracellular parasites of *** parasite could cause infection in many animals and human being and lead to sever consequences in immune-compromised *** possesses a highly polarized secretory system,and through which,parasites secret large amount of proteins outside of parasites and into host *** secretory proteins are critical for invasion and survival of ***,it is important to understand how this parasite regulates transportation of secretory proteins,biogenesis of secretory organells and protein secretion for development of therapeutic tools against *** recent findings suggest that *** has functionally repurposed evolutionarily conserved regulators of the endosomal system to the secretory pathway to transport secretory proteins and form secretory ***,it is still not clear how the biogenesis of secretory organells is regulated in *** family proteins are major mediators of vehicle fusion in eukaryotic *** this study,the function of SNARE proteins on the biogenesis of secretory organells will be investigated through conditional knockout *** components of related SNARE complex will be identified through immnoprecipitation ***,the subcellular localization of the SNAREs and their interactions will be studied to elucidate the molecular mechanism involved in the biogenesis of secretory *** findings of this study will provide a theoretical basis for the development of therapeutic measurements against ***.

关键词： Toxoplasma gondii vesicular transport SNARE STX

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Animal secretory endolysosome channel discovery

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Zoological Research 2021年第2期42卷 141-152页

作者： Yun Zhang Qi-Quan Wang Zhong Zhao Cheng-Jie Deng Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China

Secretory pore-forming proteins(PFPs) have been identified in organisms from all kingdoms of life. Our studies with the toad species Bombina maxima found an interaction network among aerolysin family PFPs(af-PFPs) and trefoil factors(TFFs). As a toad af-PFP, Bm ALP1 can be reversibly regulated between active and inactive forms, with its paralog Bm ALP3 acting as a negative regulator. Bm ALP1 interacts with Bm TFF3 to form a cellular active complex called βγ-CAT. This PFP complex is characterized by acting on endocytic pathways and forming pores on endolysosomes, including stimulating cell macropinocytosis. In addition, cell exocytosis can be induced and/or modulated in the presence of βγ-CAT. Depending on cell contexts and surroundings, these effects can facilitate the toad in material uptake and vesicular transport, while maintaining mucosal barrier function as well as immune defense. Based on experimental evidence,we hereby propose a secretory endolysosome channel(SELC) pathway conducted by a secreted PFP in cell endocytic and exocytic systems, with βγ-CAT being the first example of a SELC protein. With essential roles in cell interactions and environmental adaptations, the proposed SELC protein pathway should be conserved in other living organisms.

关键词： Pore-forming protein Secretory endolysosome channel(SELC) Endocytosis Exocytosis vesicular transport

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Drug-transporter interaction testing in drug discovery and development

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World Journal of Pharmacology 2013年第1期2卷 35-46页

作者： Peter Krajcsi Solvo Biotechnology R and D2040 BudaorsHungary

The human body consists of several physiological barriers that express a number of membrane transporters. For an orally absorbed drug the intestinal, hepatic, renal and blood-brain barriers are of the greatest importance. The ATP-binding cassette(ABC) transporters that mediate cellular efflux and the solute carrier transporters that mostly mediate cellular uptake are the two superfamilies responsible for membrane transport of vast majority of drugs and drug metabolites. The total number of human transporters in the two superfamilies exceeds 400, and about 40-50 transporters have been characterized for drug transport. The latest Food and Drug Administration guidance focuses on P-glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide 1B1(OATP1B1), OATP1B3, organic cation transporter 2(OCT2), and organic anion transporters 1(OAT1) and OAT3. The European Medicines Agency's shortlist additionally contains the bile salt export pump, OCT1, and the multidrug and toxin extrusion transporters, multidrug and toxin ex-trusion protein 1(MATE1) and MATE2/MATE2 K. A variety of transporter assays are available to test drugtransporter interactions, transporter-mediated drugdrug interactions, and transporter-mediated toxicity. The drug binding site of ABC transporters is accessible from the cytoplasm or the inner leaflet of the plasma membrane. Therefore, vesicular transport assays utilizing inside-out vesicles are commonly used assays, where the directionality of transport results in drugs being transported into the vesicle. Monolayer assays utilizing polarized cells expressing efflux transporters are the test systems suggested by regulatory agencies. However, in some monolayers, uptake transporters must be coexpressed with efflux transporters to assure detectable transport of low passive permeability drugs. For uptake transporters mediating cellular drug uptake, utilization of stable transfectants have been suggested. In vivo animal models complete t

关键词： ATP-binding cassette transporter Solute carrier Drug efflux Drug uptake Absorption-distribution-metabolism-excretion-toxicity Regulatory guidance ATPase vesicular transport Monolayer assay In vivo

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Small inhibitors of ADP-ribosylation factor activation and function in mammalian cells

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World Journal of Pharmacology 2012年第4期1卷 55-64页

作者： Sylvain G Bourgoin Mohammed-Amine El Azreq Centre de Recherche en Rhumatologie et Immunologie Centre de Recherche du CHUQ-CHUL Quebec G1V 4G2 Canada Département de Microbiologie-Infectiologie et Immunologie Faculté de Médecine Université Laval Quebec G1V 4G2 Canada

Small GTP-binding proteins of the ADP-ribosylation fac-tor （Arf） family control various cell functional responses including protein transport and recycling between different cellular compartments, phagocytosis, prolif-eration, cytoskeletal remodelling, and migration. The activity of Arfs is tightly regulated. GTPase-activating proteins （GAPs） inactivate Arfs by stimulating GTP hydrolysis, and guanine nucleotide exchange factors （GEFs） stimulate the conversion of inactive GDP-bound Arf to the active GTP-bound conformation. There is increasing evidence that Arf small GTPases contribute to cancer growth and invasion. Increased expression of Arf6 and of Arf-GEPs, or deregulation Arf-GAP functions have been correlated with enhanced invasive capacity of tumor cells and metastasis. The spatiotemporal spe-cifcity of Arf activation is dictated by their GEFs that integrate various signals in stimulated cells. Brefeldin A （BFA）, which inactivates a subset of Arf-GEFs, has been very useful for assessing the function of Golgi-localized Arfs. However, specifc inhibitors to investigate the individual function of BFA-sensitive and insensitive Arf-GEFs are lacking. In recent years, specifc screens have been developed, and new inhibitors with improved se-lectivity and potency to study cell functional responses regulated by BFA-sensitive and BFA-insensitive Arf pathways have been identified. These inhibitors have been instrumental for our understanding of the spa-tiotemporal activation of Arf proteins in cells and dem-onstrate the feasibility of developing small molecules interfering with Arf activation to prevent tumor invasion and metastasis.

关键词： Golgi vesicular transport Migration Adhe-sion Actin

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Two secretory pathways of proteins secretion

Two secretory pathways of proteins secretion

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首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Wen-Jun Hu Chao-Yu Miao Department of Pharmacology Second Military Medical University

Secretory proteins are important for physiological and pathological processes,and have significance in clinical diagnosis or *** all secretory proteins are synthesized in cytoplasm and secreted by cells,the spots where they exert their bio-functions and the ways by which they are transported to their targeting destinations are diverse from each *** pathway is a process of moving proteins from one point to another,also known as ***,the secretory pathways are generally divided into two categories,the classical secretory pathway mediated by a signal peptide(SP) which is a length of conserved amino acids present at the N-terminus of the nascent polypeptide,and the non-classical secretory pathway which is ***,with the development of secretory proteomics,more and more novel secretory proteins have come into *** lab has been dedicated in studying a novel protein—Metrnl,which is evidenced as a secretory protein with emerging ***,the secretion of proteins is important for their functional execution,and current researches have shown molecular interactions during the process,which provides a relevant sight on studying secretory ***,the understanding of the secretory pathway would be conducive to in-depth researches on functional mechanisms of the *** this review,we mainly overview the major procedure of classical secretory pathway and briefly summarize several kinds of the non-classical secretions.

关键词： secretory proteins secretory pathway ER-Golgi pathway vesicular transport

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