• Title/Summary/Keyword: trafficking

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Psychiatric Implication for the Regulation of AMPA Receptor (AMPA 수용체의 조절이 지니는 정신과적 의의)

  • Oh, Daeyoung;Lee, Eunee
    • Korean Journal of Biological Psychiatry
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    • v.20 no.1
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    • pp.1-5
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    • 2013
  • Glutamate receptors are important components of synaptic transmission in the nervous system. Especially, ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate most abundant excitatory synaptic transmission in the brain. There is elaborate mechanism of regulation of AMPA receptors including protein synthesis/degradation, intracellular trafficking, exocytosis/endocytosis and protein modification. In recent studies, it is revealed that functional dysregulation of AMPA receptors are related to major psychiatric disorders. In this review, we describe the structure and function of AMPA receptors in the synapse. We will introduce three steps of mechanism involving trafficking of AMPA receptors to neuronal membrane, lateral diffusion into synapses and synaptic retention by membrane proteins and postsynaptic scaffold proteins. Lastly, we will describe recent studies showing that regulation of AMPA receptors is important pathophysiological mechanism in psychiatric disorders.

The Golgi complex: a hub of the secretory pathway

  • Park, Kunyou;Ju, Sungeun;Kim, Nari;Park, Seung-Yeol
    • BMB Reports
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    • v.54 no.5
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    • pp.246-252
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    • 2021
  • The Golgi complex plays a central role in protein secretion by regulating cargo sorting and trafficking. As these processes are of functional importance to cell polarity, motility, growth, and division, there is considerable interest in achieving a comprehensive understanding of Golgi complex biology. However, the unique stack structure of this organelle has been a major hurdle to our understanding of how proteins are secreted through the Golgi apparatus. Herein, we summarize available relevant research to gain an understanding of protein secretion via the Golgi complex. This includes the molecular mechanisms of intra-Golgi trafficking and cargo export in the trans-Golgi network. Moreover, we review recent insights on signaling pathways regulated by the Golgi complex and their physiological significance.

Intercellular Trafficking of Homeodomain Proteins

  • Kim, Seon-Won;Moon, Jun-Yeon;Jung, Jin-Hee;Chen, Xiongyan;Shi, Chunlin;Rim, Yeong-Gil;Kwon, Hey-Jin;Jackson, David;Datla, Raju;Joliot, Alain;Kim, Jae-Yean
    • The Plant Pathology Journal
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    • v.21 no.1
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    • pp.21-26
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    • 2005
  • Homeotic proteins have pivotal roles during the development of both plant and animals. Many homeotic proteins exert control over cell fate in cells where their genes are not expressed, i.e., in a non-cell autonomous manner. Cell-to-cell communication, which delivers critical information for position-dependent specification of cell fate, is an essential biological process in multicellular organisms. In plants, there are two pathways for intercellular communication that have been identified: the ligand/receptor-mediated apoplastic pathway and the plasmodesmata-mediated symplasmic pathway. Regulatory proteins and RNAs traffic symplasmically via plasmodesmata and play a critical role in intercellular communication. Thus, the non-cell autonomous function of homeotic proteins can be explained by the recent discovery of cell-to-cell trafficking of proteins or RNAs. This article specifically focuses on understanding the intercellular movement of homeodomain proteins, a family of homeotic proteins.

Intramolecular Disulfide Bonds for Biogenesis of Calcium Homeostasis Modulator 1 Ion Channel Are Dispensable for Voltage-Dependent Activation

  • Kwon, Jae Won;Jeon, Young Keul;Kim, Jinsung;Kim, Sang Jeong;Kim, Sung Joon
    • Molecules and Cells
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    • v.44 no.10
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    • pp.758-769
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    • 2021
  • Calcium homeostasis modulator 1 (CALHM1) is a membrane protein with four transmembrane helices that form an octameric ion channel with voltage-dependent activation. There are four conserved cysteine (Cys) residues in the extracellular domain that form two intramolecular disulfide bonds. We investigated the roles of C42-C127 and C44-C161 in human CALHM1 channel biogenesis and the ionic current (ICALHM1). Replacing Cys with Ser or Ala abolished the membrane trafficking as well as ICALHM1. Immunoblotting analysis revealed dithiothreitol-sensitive multimeric CALHM1, which was markedly reduced in C44S and C161S, but preserved in C42S and C127S. The mixed expression of C42S and wild-type did not show a dominant-negative effect. While the heteromeric assembly of CALHM1 and CALHM3 formed active ion channels, the co-expression of C42S and CALHM3 did not produce functional channels. Despite the critical structural role of the extracellular cysteine residues, a treatment with the membrane-impermeable reducing agent tris(2-carboxyethyl) phosphine (TCEP, 2 mM) did not affect ICALHM1 for up to 30 min. Interestingly, incubation with TCEP (2 mM) for 2-6 h reduced both ICALHM1 and the surface expression of CALHM1 in a time-dependent manner. We propose that the intramolecular disulfide bonds are essential for folding, oligomerization, trafficking and maintenance of CALHM1 in the plasma membrane, but dispensable for the voltage-dependent activation once expressed on the plasma membrane.

Antiviral activity of methanol extract from Rhus chinensis gall (오배자 추출물의 항바이러스 활성)

  • Lee, Doseung;Min, TaeSun;Lee, Dong-Sun
    • Journal of Applied Biological Chemistry
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    • v.61 no.4
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    • pp.379-382
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    • 2018
  • Trafficking process of viral glycoprotein to cell surface results in the syncytium formation when baby hamster kidney (BHK) cells was infected by Newcastle disease virus (NDV). Rhus chinensis gall, well-known as a medicinal plant, inhibited not only syncytium formation, but also trafficking of glycoprotein, hemagglutinin-neuramidase (HN) to the cell-surface. Modification of viral glycoprotein is processed within the endoplasmic reticulum and golgi body during trafficking into surface. R. chinensis gall extracts showed the strong inhibitory activities ($IC_{50}$ $12.5{\mu}g/mL$) against ${\alpha}-glucosidase$, when compared with the ${\beta}-glucosidase$. And this inhibitory activities is increased by the samples in a dose-depedent pattern. These data showed that the extracts of R. chinensis gall inhibited the cell-surface expression of NDV-hemagglutinin-neuramidase glycoprotein without significantly affecting HN glycoprotein synthesis in NDV-infected BHK cells.

Tsg101 Is Necessary for the Establishment and Maintenance of Mouse Retinal Pigment Epithelial Cell Polarity

  • Le, Dai;Lim, Soyeon;Min, Kwang Wook;Park, Joon Woo;Kim, Youjoung;Ha, Taejeong;Moon, Kyeong Hwan;Wagner, Kay-Uwe;Kim, Jin Woo
    • Molecules and Cells
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    • v.44 no.3
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    • pp.168-178
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    • 2021
  • The retinal pigment epithelium (RPE) forms a monolayer sheet separating the retina and choroid in vertebrate eyes. The polarized nature of RPE is maintained by distributing membrane proteins differentially along apico-basal axis. We found the distributions of these proteins differ in embryonic, post-natal, and mature mouse RPE, suggesting developmental regulation of protein trafficking. Thus, we deleted tumor susceptibility gene 101 (Tsg101), a key component of endosomal sorting complexes required for transport (ESCRT), in embryonic and mature RPE to determine whether ESCRT-mediated endocytic protein trafficking correlated with the establishment and maintenance of RPE polarity. Loss of Tsg101 severely disturbed the polarity of RPE, which forms irregular aggregates exhibiting non-polarized distribution of cell adhesion proteins and activation of epidermal growth factor receptor signaling. These findings suggest that ESCRT-mediated protein trafficking is essential for the development and maintenance of RPE cell polarity.

Genomic identification and spatial expression analysis of Rab-5C-like gene identified from rock bream(Oplegnathus fasciatus)

  • Mothishri, M.S.;Umasuthan, Navaneethaiyer;Thulasitha, William Shanthakumar;Whang, Ilson;Lee, Jehee
    • Journal of fish pathology
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    • v.28 no.2
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    • pp.99-107
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    • 2015
  • Despite its economic importance as an aquaculture species, the molecular and genetic information regarding physiologically important elements in rock bream (Oplegnathus fasciatus) is not completely understood. Rab proteins play a vital role in cellular mechanisms and immunity as one of the key regulators of membrane trafficking. In this investigation, a Rab gene, named as RbRab-5C-like, was identified from Oplegnathus fasciatus. RbRab-5C-like protein exhibited high homology with Rab proteins of other species and possessed signature characteristics of Rab proteins with four conserved cysteine residues. Phylogenetic analysis showed that RbRab-5C-like clustered with other fish counterparts. The RbRab-5C-like genomic sequence possesses six exons and five introns. Transcriptional analysis revealed that RbRab-5C-like was ubiquitously expressed in all examined tissues with the highest expression occurring in the liver. While the structural and homologic characteristics of RbRab-5C-like suggest a strong conservation of this element in different species, its mRNA distribution implies a wide range of biological significance in rock bream.

A Genome-wide Scan for Selective Sweeps in Racing Horses

  • Moon, Sunjin;Lee, Jin Woo;Shin, Donghyun;Shin, Kwang-Yun;Kim, Jun;Choi, Ik-Young;Kim, Jaemin;Kim, Heebal
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.11
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    • pp.1525-1531
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    • 2015
  • Using next-generation sequencing, we conducted a genome-wide scan of selective sweeps associated with selection toward genetic improvement in Thoroughbreds. We investigated potential phenotypic consequence of putative candidate loci by candidate gene association mapping for the finishing time in 240 Thoroughbred horses. We found a significant association with the trait for Ral GApase alpha 2 (RALGAP2) that regulates a variety of cellular processes of signal trafficking. Neighboring genes around RALGAP2 included insulinoma-associated 1 (INSM1), pallid (PLDN), and Ras and Rab interactor 2 (RIN2) genes have similar roles in signal trafficking, suggesting that a co-evolving gene cluster located on the chromosome 22 is under strong artificial selection in racehorses.

The effect of intracellular trafficking of CD1d on the formation of TCR repertoire of NKT cells

  • Shin, Jung Hoon;Park, Se-Ho
    • BMB Reports
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    • v.47 no.5
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    • pp.241-248
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    • 2014
  • CD1 molecules belong to non-polymorphic MHC class I-like proteins and present lipid antigens to T cells. Five different CD1 genes (CD1a-e) have been identified and classified into two groups. Group 1 include CD1a-c and present pathogenic lipid antigens to ${\alpha}{\beta}$ T cells reminiscence of peptide antigen presentation by MHC-I molecules. CD1d is the only member of Group 2 and presents foreign and self lipid antigens to a specialized subset of ${\alpha}{\beta}$ T cells, NKT cells. NKT cells are involved in diverse immune responses through prompt and massive production of cytokines. CD1d-dependent NKT cells are categorized upon the usage of their T cell receptors. A major subtype of NKT cells (type I) is invariant NKT cells which utilize invariant $V{\alpha}14-J{\alpha}18$ TCR alpha chain in mouse. The remaining NKT cells (type II) utilize diverse TCR alpha chains. Engineered CD1d molecules with modified intracellular trafficking produce either type I or type II NKT cell-defects suggesting the lipid antigens for each subtypes of NKT cells are processed/generated in different intracellular compartments. Since the usage of TCR by a T cell is the result of antigen-driven selection, the intracellular metabolic pathways of lipid antigen are a key in forming the functional NKT cell repertoire.