• Title/Summary/Keyword: trafficking

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A WD40 Repeat Protein, Arabidopsis Sec13 Homolog 1, May Play a Role in Vacuolar Trafficking by Controlling the Membrane Association of AtDRP2A

  • Lee, Myoung Hui;Lee, Sung Hoon;Kim, Heyran;Jin, Jing Bo;Kim, Dae Heon;Hwang, Inhwan
    • Molecules and Cells
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    • v.22 no.2
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    • pp.210-219
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    • 2006
  • Dynamin-related protein 2A (AtDRP2A, formally ADL6), a member of the dynamin family, is critical for protein trafficking from the TGN to the central vacuole. However, the mechanism controlling its activity is not well understood in plant cells. We isolated Arabidopsis sec13 homolog1 (AtSeh1) that interacts with AtDRP2A by a yeast two-hybrid screening. AtSeh1 has four WD40 motifs and amino acid sequence homology to Sec13, a component of COPII vesicles. Coimmunoprecipitation and protein pull-down experiments demonstrated specific interaction between AtSeh1 and AtDRP2A. AtSeh1 bound to the pleckstrin homology domain of AtDRP2A in competition with the C-terminal domain of the latter, and this resulted in inhibition of the interaction between AtDRP2A and PtdIns3P in vitro. AtSeh1 localized to multiple locations: the nucleus, the prevacuolar compartment and the Golgi complex. Based on these results we propose that AtSeh1 plays a role in regulating cycling of AtDRP2A between membrane-bound and soluble forms.

Differential Roles of Tubby Family Proteins in Ciliary Formation and Trafficking

  • Hong, Julie J.;Kim, Kyung Eun;Park, So Young;Bok, Jinwoong;Seo, Jeong Taeg;Moon, Seok Jun
    • Molecules and Cells
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    • v.44 no.8
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    • pp.591-601
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    • 2021
  • Cilia are highly specialized organelles that extend from the cell membrane and function as cellular signaling hubs. Thus, cilia formation and the trafficking of signaling molecules into cilia are essential cellular processes. TULP3 and Tubby (TUB) are members of the tubby-like protein (TULP) family that regulate the ciliary trafficking of G-protein coupled receptors, but the functions of the remaining TULPs (i.e., TULP1 and TULP2) remain unclear. Herein, we explore whether these four structurally similar TULPs share a molecular function in ciliary protein trafficking. We found that TULP3 and TUB, but not TULP1 or TULP2, can rescue the defective cilia formation observed in TULP3-knockout (KO) hTERT RPE-1 cells. TULP3 and TUB also fully rescue the defective ciliary localization of ARL13B, INPP5E, and GPR161 in TULP3 KO RPE-1 cells, while TULP1 and TULP2 only mediate partial rescues. Furthermore, loss of TULP3 results in abnormal IFT140 localization, which can be fully rescued by TUB and partially rescued by TULP1 and TULP2. TUB's capacity for binding IFT-A is essential for its role in cilia formation and ciliary protein trafficking in RPE-1 cells, whereas its capacity for PIP2 binding is required for proper cilia length and IFT140 localization. Finally, chimeric TULP1 containing the IFT-A binding domain of TULP3 fully rescues ciliary protein trafficking, but not cilia formation. Together, these two TULP domains play distinct roles in ciliary protein trafficking but are insufficient for cilia formation in RPE-1 cells. In addition, TULP1 and TULP2 play other unknown molecular roles that should be addressed in the future.

Effect of Inhibited Rab11-FIP3 Expression on Membrane Trafficking of TRPV1 in Dorsal Root Ganglion of Rat (Rat의 후근 신경절 세포에서의 Rab11-FIP3 단백질 발현 저해가 TRPV1 채널의 세포막으로의 이동에 미치는 영향)

  • Kim, Miran;Lee, Soon-Youl
    • Microbiology and Biotechnology Letters
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    • v.40 no.3
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    • pp.278-281
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    • 2012
  • Not much is known about the membrane trafficking of TRPV1, a key player in pain transduction. Rab11-FIP3, which plays a role in various intracellular transportation pathways, has been reported to interact with TRPV1. In this study, in order to examine the role of Rab11-FIP3 in the membrane trafficking of TRPV1, Rab11-FIP3 expression in dorsal root ganglion (DRG) was inhibited using a siRNA technique. Transportation of TRPV1 to membranes was found to decrease when Rab11-FIP3 expression was inhibited, consistent with the results obtained with TRPV1-transfected HEK cells. Taken together, these results indicate that Rab11-FIP3 plays a role in the membrane trafficking of TRPV1.

LRRK2 and membrane trafficking: nexus of Parkinson's disease

  • Hur, Eun-Mi;Jang, Eun-Hae;Jeong, Ga Ram;Lee, Byoung Dae
    • BMB Reports
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    • v.52 no.9
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    • pp.533-539
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    • 2019
  • Recent evidence from genetics, animal model systems and biochemical studies suggests that defects in membrane trafficking play an important part in the pathophysiology of Parkinson's disease (PD). Mutations in leucine-rich repeat kinase 2 (LRRK2) constitute the most frequent genetic cause of both familial and sporadic PD, and LRRK2 has been suggested as a druggable target for PD. Although the precise physiological function of LRRK2 remains largely unknown, mounting evidence suggests that LRRK2 controls membrane trafficking by interacting with key regulators of the endosomal-lysosomal pathway and synaptic recycling. In this review, we discuss the genetic, biochemical and functional links between LRRK2 and membrane trafficking. Understanding the mechanism by which LRRK2 influences such processes may contribute to the development of disease-modifying therapies for PD.

Phosphoinositide turnover in Toll-like receptor signaling and trafficking

  • Le, Oanh Thi Tu;Nguyen, Tu Thi Ngoc;Lee, Sang Yoon
    • BMB Reports
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    • v.47 no.7
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    • pp.361-368
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    • 2014
  • Lipid components in biological membranes are essential for maintaining cellular function. Phosphoinositides, the phosphorylated derivatives of phosphatidylinositol (PI), regulate many critical cell processes involving membrane signaling, trafficking, and reorganization. Multiple metabolic pathways including phosphoinositide kinases and phosphatases and phospholipases tightly control spatio-temporal concentration of membrane phosphoinositides. Metabolizing enzymes responsible for PI 4,5-bisphosphate (PI(4,5)P2) production or degradation play a regulatory role in Toll-like receptor (TLR) signaling and trafficking. These enzymes include PI 4-phosphate 5-kinase, phosphatase and tensin homolog, PI 3-kinase, and phospholipase C. PI(4,5)P2 mediates the interaction with target cytosolic proteins to induce their membrane translocation, regulate vesicular trafficking, and serve as a precursor for other signaling lipids. TLR activation is important for the innate immune response and is implicated in diverse pathophysiological disorders. TLR signaling is controlled by specific interactions with distinct signaling and sorting adaptors. Importantly, TLR signaling machinery is differentially formed depending on a specific membrane compartment during signaling cascades. Although detailed mechanisms remain to be fully clarified, phosphoinositide metabolism is promising for a better understanding of such spatio-temporal regulation of TLR signaling and trafficking.

A discussion on the issues of human trafficking and global economy, HIV, and inhumanity: A case study of Nepal women (인신매매와 관련된 국제경제, HIV, 그리고 비인간적 문제들에 대한 담론: 네팔여성들에 대한 사례제시를 중심으로)

  • Jang, Duck-Hyung
    • Korean Security Journal
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    • no.46
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    • pp.171-187
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    • 2016
  • Human trafficking is a booming underground business and is the fastest growing and criminal activity in today's society. The use of coercion or fraud marks the territory of trafficking. Most people trafficked suffer constant threats, violence, and forced acts while imprisoned by their traffickers. Such human trafficking entails significant problems not only for the victims but also for the economies and community health. Large corporations overseas have also been known to partake in the sex slave industry. Another hidden cost to the global economy is the cost of law enforcement and anti-trafficking measures being implemented. Further, sex Trafficking carries many potential health consequences, one of the biggest risks is HIV infection. That means, sex trafficking is an engine of the global AIDS epidemic with one study portraying nearly fifty six percent of all sex slaves having HIV or AIDS. Therefore, many of people are being infected with HIV and many other diseases every day through contact with the sex slave industry costing millions to society and the global economy. in this study, the author presents a case study of trafficking against Nepalese women. Nepalese women being trafficked are found to have a high prevalence of HIV infection. In conclusion and discussion, a few of solutions needed to be addressed for controling human trafficking for sex slavery suggested.

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Research on John School as a policy to prevent recidivism of online sex trafficking

  • Park, Jong-Ryeol;Noe, Sang-Ouk
    • Journal of the Korea Society of Computer and Information
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    • v.23 no.8
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    • pp.143-149
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    • 2018
  • Recently, President Donald Trump signed FOSTA (Fight Online Sex Trafficking Act) in April 11, 2018, which makes online service no more immune from civil liability for the action of third party facilitating sex trafficking content. Although it is also important to enhance security regulations and cognition on law, but it will be economically more effective to put more energy on preventing recidivism. For John School in Korea, it should increase implementation rate by putting core manpower and budget for preventing needs of sex purchase and then, check operation method and efficacy to improve the actual program. One way is first, empirical analysis and data is required on efficacy of John School program. Second, should have clear definition in Special Sex Trade Law. Third, more strick regulation for selecting participant is required. Fourth, more manpower and budget is required. Fifth, charging the participant for educational fee shall be reviewed. Sixth, educational program should be reviewed. The most important point of education is to make those criminals feel guilty about financially purchasing the sex, basically making them to recognize that it is ethically wrong. However, the current education system contains no clear explanation about the ethical issue of such problem but focusing more on other factors such as sexual disease and structural problem of sexual business. Therefore, this failed to deliver the right psychological training to those criminals without any ethical control. Knowing why women feel hurt when having unwanted sexual relationship by being paid is required part in terms of education for preventing sex trafficking.

Role of Rab11 on Membrane Trafficking of Rat Vanilloid Receptor, TRPV1 (바닐로이드 수용체 TRPV1의 막수송과정에서의 Rab11의 역할)

  • Um, Ki-Bum;Lee, Soon-Youl
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.7
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    • pp.3096-3102
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    • 2011
  • Vanilloid receptor, TRPV1 (transient receptor potential vanilloid 1) is a non-selective cation channel that responds to a variety of pain-eliciting material including capsaicin, pH, heat. Although, membrane trafficking of TRPV1 was not much known so far, TRPV1 was reported to interact with FIP3 (family of Rab11 interacting protein 3). FIP3 was identified as one of Rab11 interacting proteins that is recently reported important in membrane trafficking of several channel proteins directly or indirectly. Therefore, in this study, we examined the role of Rab11 in the membrane trafficking of TRPV1 using cell biological and biochemical techniques. Rab11 was found really colocalized with TRPV1 based on the result of confocal microscopy. However, GST-pulldown assay, one of biochemical technique, found that Rab11 did not interact with TRPV1. Although Rab11 does not interact with TRPV1 directly, we hypothesized that Rab11 is indeed involved in the membrane trafficking of TRPV1. In order to examine further the role of Rab11 in the membrane trafficking of TRPV1, the expression of TRPV1 on the membrane was examined when the expression of Rab11 was decreased down to about 50% by siRNA technique and found decreased significantly. From this result, we can conclude that Rab11 is involved in the membrane trafficking of TRPV1 in a way of including FIP3.

Protection of aquo/hydroxocobalamin from reduced glutathione by a B12 trafficking chaperone

  • Jeong, Jin-Ju;Ha, Tal-Soo;Kim, Ji-Hoe
    • BMB Reports
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    • v.44 no.3
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    • pp.170-175
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    • 2011
  • We identified a bovine $B_{12}$ trafficking chaperone bCblC in Bos taurus that showed 88% amino acid sequence identity with a human homologue. The protein bCblC was purified from E. coli by over-expression of the encoding gene. bCblC bound cyanocobalamin (CNCbl), methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) in the base-off states and eliminated the upper axial ligands forming aquo/hydroxocobalamin ($OH_2$/OHCbl) under aerobic conditions. A transition of $OH_2$/OHCbl was induced upon binding to bCblC. Interestingly, bCblC-bound $OH_2$/OHCbl did not react with reduced glutathione (GSH), while the reaction of free$OH_2$/OHCbl with GSH resulted in the formation of glutathionylcobalamin (GSCbl) and glutathione disulfide (GSSG). Furthermore we found that bCblC eliminates the GSH ligand of GSCbl forming $OH_2$/OHCbl. The results demonstrated that bCblC is a $B_{12}$ trafficking chaperone that binds cobalamins and protects $OH_2$/OHCbl from GSH, which could be oxidized to GSSG by free $OH_2$/OHCbl.