• Title/Summary/Keyword: Endocytosis

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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.

Huntingtin-interacting protein 1-related is required for accurate congression and segregation of chromosomes

  • Park, Sun-Joo
    • BMB Reports
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    • v.43 no.12
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    • pp.795-800
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    • 2010
  • Huntingtin-interacting protein 1-related (HIP1r) is known to function in clathrin-mediated endocytosis and regulation of the actin cytoskeleton, which occurs continuously in non-dividing cells. This study reports a new function for HIP1r in mitosis. Green fluorescent protein-fused HIP1r localizes to the mitotic spindles. Depletion of HIP1r by RNA interference induces misalignment of chromosomes and prolonged mitosis, which is associated with decreased proliferation of HIP1r-deficeint cells. Chromosome misalignment leads to missegregation and ultimately production of multinucleated cells. Depletion of HIP1r causes persistent activation of the spindle checkpoint in misaligned chromosomes. These findings suggest that HIP1r plays an important role in regulating the attachment of spindle microtubules to chromosomes during mitosis, an event that is required for accurate congression and segregation of chromosomes. This finding may provide new insights that improve the understanding of various human diseases involving HIP1r as well as its fusion genes.

Self-organized Nanogels of Polysaccharide Derivatives in Anti-Cancer Drug Delivery

  • Park, Sin-Jung;Na, Kun
    • Journal of Pharmaceutical Investigation
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    • v.40 no.4
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    • pp.201-212
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    • 2010
  • Self-organized nanogels from polysaccharide derivatives offer a promising approach in treatment of cancer due to their flexibility in chemistry and their ability to improve the therapeutic index of a drug by modifying biodistribution by their preferential localization at target sites and lower distribution in normal healthy tissues. These properties have promoted studies of active cancer targeting by self-organized nanogels for even better accumulation in solid tumors. However although many researchers have reported their potential by using cell culture systems and small animal tumor models in cancer therapy, these nanogels need more decoration such as conjugation with targeting moiety and endowment of stimuli-sensitivity for precise targeting of the cancer site. In this review, we summarize the recent efforts in developing novel targeting approaches via active endocytosis and stimuli-sensitive systems responding to hyperthermic or acidic tumor pH conditions.

Biochemical Analysis of Anagrapha falcifera NPV Attachment to Spodoptera frugiperda 21 Cells

  • PARK, JIN O;JAI MYUNG YANG;IN SIK CHUNG
    • Journal of Microbiology and Biotechnology
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    • v.9 no.3
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    • pp.361-364
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    • 1999
  • The binding characteristics of Anagrapha falcifera nuclear polyhedrosis virus (AtNPV) to Spodoptera frugiperda 21 (Sf21) cells were investigated. The cells displayed an affinity of 4.7×10/sup 10/M/sup -1/ with about 3,300 binding sites per cell. The biochemical nature of the AfNPV-binding sites on the cell surface was also partially identified. Our findings suggest that the binding-site moiety has a glycoprotein component, but that the direct involvement of oligosacccharides containing N-acetylglucosamine or sialic acid residues in binding is unlikely, and that AfNPV entry into Sf21 cells may be via receptor-mediated endocytosis.

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Ultrastructural Changes at the Surfaces of Oocytes during Oogenesis of the starfish, Asterina pectinifera (Muller and Troschel) (별불가사리(Asterinapectinifera)의 난자형성 과정 중 난모세포 표면의 미세구조적 변화)

  • 이양림;한지원
    • The Korean Journal of Zoology
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    • v.37 no.2
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    • pp.203-212
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    • 1994
  • 별불가사리 난자형성 중 난모세포(직경 7-l7O Um) 표면의 구조적 변화를 투과 전자현미경으로 관찰하였다. 직경 25-855 Um의 난모세포에서 'endocvtosis'와 관련된 구조인 coated pit, coated vesicle과 내포소낭이 존재하였으며. 내포소낭은 난황립과 융합하였다. 특히, 이러한 융합은 직경 130-155 Um의 난모세포에서 많이 관찰되었다 난자형성 초기에 난모세포의 미세융모는 세포막을 따라 무질서하게 분포하고. 인접한 세포와 맞닿아 있었다. 직경 15 Um에서 65 Um에 이르는 난모세포는 세포막 부위에 따라서 미세융모의 굵기와 길이, 그리고 형태가 다르게 나타났고, 직경 100 Um 이상의 난모세포에서는 잘 발달된 미세음모가 난뢍층에 존재하였다 여포세포로부터 나온 돌기는 직경 7 Um의 난모세포와 난자형성 후기의 난모세포에서 난황층을 윤고 세포막과 닿아 'junctional complex'를 형성하였다. 이와같은 난모세포 표면의 다양한 구조적 변화는 난모세포의 세포막을 통한 물질투과 기능의 분화와 관련이 있을 것으로 생각된다.

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Activities of Recombinant MT1-MMP Expressed in PANC-1 Cells. (PANC-1세포에서 발현된 재조합 MT1-MMP의 효소 활성)

  • Kim, Hye-Nan;Chung, Hye-Shin
    • Journal of Life Science
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    • v.18 no.3
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    • pp.422-425
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    • 2008
  • Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-associated zinc-dependent endoproteinase involved in extracellular matrix remodeling. MT1-MMP hydrolyzes ECM proteins like collagen and is involved in cancer cell migration and metastasis. Caveolins are integral membrane proteins and play a role in formation of caveolae, specialized membrane microdomains involved in clathrin-independent endocytosis. Recombinant MT1-MMP was transiently expressed in PANC-1 cells. Cells expressing recombinant MT1-MMP were able to hydrolyze collagen and migrate on collagen coated trans-well. Both subjacent collagen degradation and the cell migration conferred by recombinant MT1-MMP were inhibited by co-transfection of plasmids containing caveolin-1 cDNA. The results support that MT1-MMP is localized in lipid raft of the membrane and MT1-MMP activities in invasive cells could be inhibited by caveolin.

Glucose Transporters and Insulin Action : Some Insights into Diabetes Management

  • Jung, Chan-Y.;Lee, Wan
    • Archives of Pharmacal Research
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    • v.22 no.4
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    • pp.329-334
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    • 1999
  • Insulin stimulates glucose uptake in muscle and adipose cells primarily by recruiting GLUT4 from an intracellular storage pool to the plasma membrane. Dysfunction of this process known as insulin resistance causes hyperglycemia, a hallmark of diabetes and obesity. Thus the understanding of the mechanisms underlying this process at the molecular level may give an insight into the prevention and treatment of these health problems. GLUT4 in rat adipocytes, for example, constantly recycles between the cells surface and an intracellular pool by endocytosis and exocytosis, each of which is regulated by an insulin-sensitive and GLUT4-selective sorting mechanism. Our working hypothesis has been that this sorting mechanism includes a specific interaction of a cytosolic protein with the GLUT4 cytoplasmic domain. Indeed, a synthetic peptide of the C-terminal cytoplasmic domain of GLUT4 induces an insulin-like GLUT4 recruitment when introduced in rat adipocytes. Relevance of these observations to a novel euglycemic drug design is discussed.

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Biophysical effect of lipid modification at palmitoylation site on the structure of Caveolin 3

  • Ma, Yu-Bin;Kang, Dong-Hoon;Kim, Myeongkyu;Kim, Ji-Hun
    • Journal of the Korean Magnetic Resonance Society
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    • v.23 no.3
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    • pp.67-72
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    • 2019
  • Caveolae are small plasma membrane invaginations that play many roles in signal transduction, endocytosis, mechanoprotection, lipid metabolism. The most important protein in caveolae is the integral membrane protein, caveolin, which is divided into three families such as caveolin 1, caveolin 2, and caveolin 3. Caveolin 1 and 3 are known to incorporate palmitate through linkage to three cysteine residues. Regulation of the protein palmitoylation cycle is important for the cellular processes such as intracellular localization of the target protein, membrane association, conformation, protein-protein interaction, and activity. However, the detailed aspect of individual palmitoylation has not been studied. In the present work, the role of each lipid modification at three cysteines was studied by NMR. Our results suggest that each lipid modification at the natively palmitoylation site has its own roles. For example, lipidations to C106 and C129 are play a role in structural stabilization, however, interestingly, lipid modification to C116 interrupts the structural stabilization.

Activation of the M1 Muscarinic Acetylcholine Receptor Induces GluA2 Internalization in the Hippocampus (쥐 해마에서 M1 무스카린 아세틸콜린 수용체의 활성에 의한 GluA2 세포내이입 연구)

  • Ryu, Keun Oh;Seok, Heon
    • Journal of Life Science
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    • v.25 no.10
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    • pp.1103-1109
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    • 2015
  • Cholinergic innervation of the hippocampus is known to be correlated with learning and memory. The cholinergic agonist carbachol (CCh) modulate synaptic plasticity and produced long-term synaptic depression (LTD) in the hippocampus. However, the exact mechanisms by which the cholinergic system modifies synaptic functions in the hippocampus have yet to be determined. This study introduces an acetylcholine receptor-mediated LTD that requires internalization of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors on the postsynaptic surface and their intracellular mechanism in the hippocampus. In the present study, we showed that the application of the cholinergic agonist CCh reduced the surface expression of GluA2 on synapses and that this reduction was prevented by the M1 muscarinic acetylcholine receptor antagonist pirenzepine in primary hippocampal neurons. The interaction between GluA2 and the glutamate receptor-interacting protein 1 (GRIP1) was disrupted in a hippocampal slice from a rat upon CCh simulation. Under the same conditions, the binding of GluA2 to adaptin-α, a protein involved in clathrin-mediated endocytosis, was enhanced. The current data suggest that the activation of LTD, mediated by the acetylcholine receptor, requires the internalization of the GluA2 subunits of AMPA receptors and that this may be controlled by the disruption of GRIP1 in the PDZ ligand domain of GluA2. Therefore, we can hypothesize that one mechanism underlying the LTD mediated by the M1 mAChR is the internalization of the GluA2 AMPAR subunits from the plasma membrane in the hippocampal cholinergic system.

Ultrastructural Studies of Vitellogenesis According to Germ Cell Development, and Mating Period and Spawning Activity in Female Rapa Whelk, Rapana venosa (Gastropoda: Muricidae) in the Brackish Water Area of Seomjin River, Korea (한국 섬진강 기수역 암컷 피뿔고둥 Rapana venosa (복족류 : 뿔소라과)의 생식세포 발달에 따른 난황형성과정의 미세구조적 연구 및 교미 시기와 산란 활성)

  • SON, Pal-Won;LEE, Il-Ho;KIM, Sung-Han
    • Journal of Fisheries and Marine Sciences Education
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    • v.27 no.4
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    • pp.1031-1040
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    • 2015
  • Ultrstructural studies of germ cell differentiation and vitellogenesis in the oocytes of the female Rapana venosa in the brackish water area of Seomjin River were investigated by transmission electron microscope observations. In the early vitellogenic oocytes, the Golgi complex and mitochondria were involved in the formation of glycogen particle, lipid droplets, and yolk granules. In the late vitellogenic oocytes, the rough endoplasmic reticulum and multivesicular bodies were involved in the formation of proteid yolk granules in the cytoplasm. However, heterosynthetic vitellogenesis in this species were not observed in vitellogenic oocytes during oogenesis. A mature yolk granule was composed of three components: crystalline core, electron lucent cortex and the limiting membrane. As shown in some large gastropods, vitellogenesis in R. venosa occurred by way of endogenous autosynthesis without heterosythetic vitellogenesis (exogeneous endocytosis), which are found in the oocytes in bivalves. The mating period and spawning activity were related with the increases of seawater temperatures and salinities.