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The molecular chaperone Hsp90 maintains Golgi organization and vesicular trafficking by regulating microtubule stability

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Journal of Molecular Cell Biology 2020年第6期12卷 448-461页

作者： Yuan Wu Yubo Ding Xiudan Zheng Kan Liao Key Laboratory of Systems Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Hsp90 is an abundant and special molecular chaperone considered to be the regulator of many transcription factors and signaling kinases. Its high abundance is indicative of its involvement in some more fundamental processes. In this study, we provide evidence that Hsp90 is required for microtubule stabilization, Golgi organization, and vesicular trafficking. We showed that Hsp90 is bound to microtubule-associated protein 4 (MAP4), which is essential for maintaining microtubule acetylation and stabilization. Hsp90 depletion led to the decrease in MAP4, causing microtubule deacetylation and destabilization. Furthermore, in Hsp90-depleted cells, the Golgi apparatus was fragmented and anterograde vesicle trafficking was impaired, with phenotypes similar to those induced by silencing MAP4. These disruptive effects of Hsp90 depletion could be rescued by the expression of exogenous MAP4 or the treatment of trichostatin A that increases microtubule acetylation as well as stability. Thus, microtubule stability is an essential cellular event regulated by Hsp90.

关键词： Hsp90 microtubule Golgi fragmentation vesicular trafficking MAP4

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Dynamic localization of hepatocellular transporters in health and disease

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World Journal of Gastroenterology 2008年第44期14卷 6786-6801页

作者： Marcelo G Roma Fernando A Crocenzi Aldo D Mottino Instituto de Fisiología Experimental (IFISE)-Facultad de Ciencias Bioquímicasy Farmacéuticas (CONICET-U.N.R.) S2002LRLRosarioArgentina

Vesicle-based traffi cking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal,submembrane compartment,followed by exocytic targeting to the plasma membrane. Once delivered to the plasma membrane,the transporters usually undergo recycling between the plasma membrane and the endosomal compartment,which usually serves as a reservoir of pre-existing transporters available on demand. The balance between exocytic targeting and endocytic internalization from/to this recycling compartment is therefore a chief determinant of the overall capability of the liver epithelium to secrete bile and to detoxify endo and xenobiotics. Hence,it is a highly regulated process. Impaired regulation of this balance may lead to abnormal localization of these transporters,which results in bile secretory failure due to endocytic internalization of key transporters involved in bile formation. This occurs in several experimental models of hepatocellular cholestasis,and in most human cholestatic liver diseases. This review describes the molecular bases involved in the biology of the dynamic localization of hepatocellular transporters and its regulation,with a focus on the involvement of signaling pathways in this process. Their alterations in different experimental models of cholestasis and in human cholestatic liver disease are reviewed. In addition,the causes explaining the pathological condition (e.g. disorganization of actin or actin-transporter linkers) and the mediators involved (e.g. activation of cholestatic signaling transduction pathways) are also discussed. Finally,several experimental therapeutic approaches based upon the administration of compounds known to stimulate exocytic insertion of canalicular transporters (e.g. cAMP,tauroursodeoxycholate) are described.

关键词： Hepatocellular transporters Cholestasis cAMP Bile salts vesicular trafficking Endocytosis Signaling pathways

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vesicular transport-related genes in Diaphorina citri are involved in the process of Candidatus Liberibacter asiaticus infection

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Journal of Integrative Agriculture 2024年第12期23卷 4136-4146页

作者： Yingzhe Yuan Tao Peng Aijun Huang Jun He Chenyang Yuan Tianyuan Liu Long Yi Xuejin Cui Xuefeng Wang Changyong Zhou National Citrus Engineering and Technology Research Center Citrus Research InstituteSouthwest UniversityChongqing 400712China College of Life Sciences Yulin CollegeYulin 719000China National Navel Orange Engineering Research Center Gannan Normal UniversityGanzhou 341000China Key Laboratory of Entomology and Pest Control Engineering College of Plant ProtectionSouthwest UniversityChongqing 400715China

Asian citrus psyllid(ACP,Diaphorina citri)is the major vector of Candidatus Liberibacter asiaticus(CLas),which is a bacterial pathogen causing the devastating citrus Huanglongbing(HLB)*** citri is known to carry CLas in a persistent and propagative *** studies have suggested that CLas may use the vesicular structures of *** cells as its propagation ***,the mechanisms by which CLas enters the *** cells and how vesicle-mediated trafficking is involved remain *** this study,we monitored the titer change of CLas in *** nymphs during the process of CLas acquisition from feeding on infected citrus *** found that the titer of CLas increased with the acquisition access *** infection,there was a significant upregulation in the expression of several vesicular transport-related genes in *** titer of CLas was significantly reduced in the midgut and whole insect body when endocytosis and the endosome network in *** were ***,silencing the *** clathrin-heavy chain gene also led to a reduction in the CLas titer in *** results suggest that CLas infection upregulates the genes related to vesicular transport in ***,which facilitates the invasion of endocytosis-dependent pathogens.

关键词： Huanglongbing endocytosis vesicular trafficking CLas acquisition

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Endosomal trafficking defects in patient cells with KIAA1109 biallelic variants

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Genes & Diseases 2019年第1期6卷 56-67页

作者： Megan S.Kane Callie J.Diamonstein Natalie Hauser John F.Deeken John E.Niederhuber Thierry Vilboux Inova Translational Medicine Institute Inova Health SystemFairfaxVAUnited States Department of Medicine Virginia Commonwealth UniversityRichmondVAUnited States Department of Public Health Sciences University of Virginia School of MedicineCharlottesvilleVAUnited States Department of Oncology and Surgery Johns Hopkins University School of MedicineBaltimoreMDUnited States

The uncharacterized gene KIAA1109 has recently been associated with a congenital neurological malformation disorder that variably presents with arthrogryposis,craniofacial and/or cardiac *** have identified two additional patients with compound heterozygous KIAA1109 variants presenting with the same neurological *** mechanism whereby KIAA1109 loss of function causes this spectrum of disorders was the primary focus of our *** hypothesized that KIAA1109 function could be conserved relative to the fly gene tweek and examined endocytosis and endosome recycling in patient ***,we examined the structure of the cytoskeleton and cilia based on functional overlap with endocytosis and several known etiologies for neuronal migration *** primary dermal fibroblasts from one patient and a healthy donor,we performed immunofluorescence and endocytosis assays to examine the endosomal,cytoskeletal,and ciliary cellular *** found notable abnormalities in endosomal trafficking and endosome recycling *** also observed changes in the actin cytoskeleton and cilia structural *** conclude that the function of KIAA1109 in humans may indeed overlap with the function of the Drosophila ortholog,resulting in perturbations to endosomal trafficking and the actin *** alterations have ripple effects,altering many pathways that are critical for proper neuronal migration and embryonic development.

关键词： Cilia Endocytosis KIAA1109 Neurological malformation vesicular trafficking

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