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JOURNAL ARTICLE
Andrea Bugarcic, Irina Vetter, Silke Chalmers, Genevieve Kinna, Brett M Collins, Rohan D Teasdale
Retromer is a trimeric complex composed of Vps26, Vps29, and Vps35 and has been shown to be involved in trafficking and sorting of transmembrane proteins within the endosome. The Vps26 paralog, Vps26B, defines a distinct retromer complex (Vps26B-retromer) in vivo and in vitro. Although endosomally associated, Vps26B-retromer does not bind the established retromer transmembrane cargo protein, cation-independent mannose 6-phosphate receptor (CI-M6PR), indicating it has a distinct role to retromer containing the Vps26A paralog...
November 2015: Cell Biology International
#22
JOURNAL ARTICLE
Matteo Da Ros, Noora Hirvonen, Opeyemi Olotu, Jorma Toppari, Noora Kotaja
Spermatozoa are produced during spermatogenesis as a result of mitotic proliferation, meiosis and cellular differentiation. Postmeiotic spermatids are exceptional cells given their haploid genome and remarkable sperm-specific structural transformations to compact and reshape the nucleus and to construct the flagellum and acrosome. These processes require delicate coordination and active communication between distinct cellular compartments. In this study, we elucidated the interplay between the haploid RNA regulation and the vesicular transport system...
February 5, 2015: Molecular and Cellular Endocrinology
#23
JOURNAL ARTICLE
Emil K Gustavsson, Ilaria Guella, Joanne Trinh, Chelsea Szu-Tu, Alex Rajput, Ali H Rajput, John C Steele, Martin McKeown, Beom S Jeon, Jan O Aasly, Matthew J Farrer
BACKGROUND: A pathogenic mutation (VPS35 p.D620N) within the retromer complex has been shown to segregate with late-onset Parkinson's disease (PD). Several studies have subsequently detected the mutation in patients with PD and not in controls. METHODS: Mutation screening of the coding regions of the retromer cargo recognition complex genes (VPS26A/B, VPS29, and VPS35) was carried out in patients with PD (n = 396), atypical parkinsonism (n = 229), and in 368 controls...
April 2015: Movement Disorders: Official Journal of the Movement Disorder Society
#24
JOURNAL ARTICLE
M Althubiti, L Lezina, S Carrera, R Jukes-Jones, S M Giblett, A Antonov, N Barlev, G S Saldanha, C A Pritchard, K Cain, S Macip
Cellular senescence is a terminal differentiation state that has been proposed to have a role in both tumour suppression and ageing. This view is supported by the fact that accumulation of senescent cells can be observed in response to oncogenic stress as well as a result of normal organismal ageing. Thus, identifying senescent cells in in vivo and in vitro has an important diagnostic and therapeutic potential. The molecular pathways involved in triggering and/or maintaining the senescent phenotype are not fully understood...
November 20, 2014: Cell Death & Disease
#25
JOURNAL ARTICLE
Matthew Gallon, Thomas Clairfeuille, Florian Steinberg, Caroline Mas, Rajesh Ghai, Richard B Sessions, Rohan D Teasdale, Brett M Collins, Peter J Cullen
The sorting nexin 27 (SNX27)-retromer complex is a major regulator of endosome-to-plasma membrane recycling of transmembrane cargos that contain a PSD95, Dlg1, zo-1 (PDZ)-binding motif. Here we describe the core interaction in SNX27-retromer assembly and its functional relevance for cargo sorting. Crystal structures and NMR experiments reveal that an exposed β-hairpin in the SNX27 PDZ domain engages a groove in the arrestin-like structure of the vacuolar protein sorting 26A (VPS26A) retromer subunit. The structure establishes how the SNX27 PDZ domain simultaneously binds PDZ-binding motifs and retromer-associated VPS26...
September 2, 2014: Proceedings of the National Academy of Sciences of the United States of America
#26
JOURNAL ARTICLE
Barbara Shannon, Alexandra Soto-Ortolaza, Sruti Rayaprolu, Heather D Cannon, Catherine Labbé, Bruno A Benitez, Jiyoon Choi, Timothy Lynch, Magdalena Boczarska-Jedynak, Grzegorz Opala, Anna Krygowska-Wajs, Maria Barcikowska, Jay A Van Gerpen, Ryan J Uitti, Wolfdieter Springer, Carlos Cruchaga, Zbigniew K Wszolek, Owen A Ross
We recently showed that mutation of the VPS35 gene can cause late-onset Parkinson's disease. In the present study we sequenced 702 affected subjects from the Mayo Clinic Parkinson's disease patient-control series for the VPS29 and VPS26A/B genes. We identified only 2 rare nonsynonymous variants in the VPS26A p.K93E and VPS29 p.N72H. The results show that mutations in the genes composing the retromer cargo recognition subunit are not a common cause of Parkinson's disease.
August 2014: Neurobiology of Aging
#27
JOURNAL ARTICLE
Eva Koschmidder, Brit Mollenhauer, Meike Kasten, Christine Klein, Katja Lohmann
VPS35 mutations have been identified as a cause of autosomal dominantly inherited Parkinson's disease (PD). VPS35 interacts with VPS26A in the retromer complex that links mitochondrial and lysosomal pathways, which have both been shown to be dysfunctional in PD. Thus, mutations in VPS26A may be associated with PD. To test this hypothesis, we screened 245 idiopathic PD patients and 185 control subjects for mutations in the retromer subunit VPS26A. We found 2 novel missense variants in patients and 2 known missense variants in control subjects...
June 2014: Neurobiology of Aging
#28
JOURNAL ARTICLE
Jordan Follett, Suzanne J Norwood, Nicholas A Hamilton, Megha Mohan, Oleksiy Kovtun, Stephanie Tay, Yang Zhe, Stephen A Wood, George D Mellick, Peter A Silburn, Brett M Collins, Andrea Bugarcic, Rohan D Teasdale
The retromer is a trimeric cargo-recognition protein complex composed of Vps26, Vps29 and Vps35 associated with protein trafficking within endosomes. Recently, a pathogenic point mutation within the Vps35 subunit (D620N) was linked to the manifestation of Parkinson's disease (PD). Here, we investigated details underlying the molecular mechanism by which the D620N mutation in Vps35 modulates retromer function, including examination of retromer's subcellular localization and its capacity to sort cargo. We show that expression of the PD-linked Vps35 D620N mutant redistributes retromer-positive endosomes to a perinuclear subcellular localization and that these endosomes are enlarged in both model cell lines and fibroblasts isolated from a PD patient...
February 2014: Traffic
#29
JOURNAL ARTICLE
Martijn van de Bunt, Kyle J Gaulton, Leopold Parts, Ignasi Moran, Paul R Johnson, Cecilia M Lindgren, Jorge Ferrer, Anna L Gloyn, Mark I McCarthy
Recent advances in the understanding of the genetics of type 2 diabetes (T2D) susceptibility have focused attention on the regulation of transcriptional activity within the pancreatic beta-cell. MicroRNAs (miRNAs) represent an important component of regulatory control, and have proven roles in the development of human disease and control of glucose homeostasis. We set out to establish the miRNA profile of human pancreatic islets and of enriched beta-cell populations, and to explore their potential involvement in T2D susceptibility...
2013: PloS One
#30
JOURNAL ARTICLE
Shuangyan Lu, Yan Xie, Kun Lin, Siwei Li, Yidan Zhou, Pei Ma, Zhihua Lv, Xin Zhou
PURPOSE: Several novel genetic variants for type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWAS). A case-controll study was performed to investigate the association of five new European or South Asian GWAS-derived susceptibility loci with T2DM in a Chinese population. METHODS: Five single nucleotide polymorphisms (SNPs) were genotyped: rs3923113 near GRB14, rs16861329 in ST6GAL1, rs1802295 in VPS26A, rs7178572 in HMG20A, and rs231362 near KCNQ1, by high-resolution melting (HRM) of small amplicons...
2012: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
#31
JOURNAL ARTICLE
Hisashi Fukuda, Minako Imamura, Yasushi Tanaka, Minoru Iwata, Hiroshi Hirose, Kohei Kaku, Hiroshi Maegawa, Hirotaka Watada, Kazuyuki Tobe, Atsunori Kashiwagi, Ryuzo Kawamori, Shiro Maeda
AIMS: The DUSP9 locus on chromosome X was identified as a susceptibility locus for type 2 diabetes in a meta-analysis of European genome-wide association studies (GWAS), and GWAS in South Asian populations identified 6 additional single nucleotide polymorphism (SNP) loci for type 2 diabetes. However, the association of these loci with type 2 diabetes have not been examined in the Japanese. We performed a replication study to investigate the association of these 7 susceptibility loci with type 2 diabetes in the Japanese population...
2012: PloS One
#32
JOURNAL ARTICLE
Andrea Bugarcic, Yang Zhe, Markus C Kerr, John Griffin, Brett M Collins, Rohan D Teasdale
The trimeric Vps29-Vps35-Vps26 sub-complex of retromer mediates retrograde transport of transmembrane proteins from endosomes to the trans-Golgi network. Our group has recently identified a Vps26 paralogue, Vps26B, which is able to suppress the expression of Vps26A when exogenously expressed in mammalian cells and defines a distinct retromer complex (Vps26B-retromer) in vivo and in vitro. In this study, we use HEK293 cells stably expressing either Vps26A-myc or Vps26B-myc to address the role of retromer cargo transport and subcellular localization of the two core retromer complexes as defined by the two mammalian-specific Vps26 paralogues...
December 2011: Traffic
#33
JOURNAL ARTICLE
Jaspal S Kooner, Danish Saleheen, Xueling Sim, Joban Sehmi, Weihua Zhang, Philippe Frossard, Latonya F Been, Kee-Seng Chia, Antigone S Dimas, Neelam Hassanali, Tazeen Jafar, Jeremy B M Jowett, Xinzhong Li, Venkatesan Radha, Simon D Rees, Fumihiko Takeuchi, Robin Young, Tin Aung, Abdul Basit, Manickam Chidambaram, Debashish Das, Elin Grundberg, Asa K Hedman, Zafar I Hydrie, Muhammed Islam, Chiea-Chuen Khor, Sudhir Kowlessur, Malene M Kristensen, Samuel Liju, Wei-Yen Lim, David R Matthews, Jianjun Liu, Andrew P Morris, Alexandra C Nica, Janani M Pinidiyapathirage, Inga Prokopenko, Asif Rasheed, Maria Samuel, Nabi Shah, A Samad Shera, Kerrin S Small, Chen Suo, Ananda R Wickremasinghe, Tien Yin Wong, Mingyu Yang, Fan Zhang, Goncalo R Abecasis, Anthony H Barnett, Mark Caulfield, Panos Deloukas, Timothy M Frayling, Philippe Froguel, Norihiro Kato, Prasad Katulanda, M Ann Kelly, Junbin Liang, Viswanathan Mohan, Dharambir K Sanghera, James Scott, Mark Seielstad, Paul Z Zimmet, Paul Elliott, Yik Ying Teo, Mark I McCarthy, John Danesh, E Shyong Tai, John C Chambers
We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4...
August 28, 2011: Nature Genetics
#34
JOURNAL ARTICLE
Sang-Je Park, Jae-Won Huh, Young-Hyun Kim, Ji-Su Kim, Bong-Seok Song, Sang-Rae Lee, Sun-Uk Kim, Heui-Soo Kim, Kazuhiko Imakawa, Kyu-Tae Chang
The retromer complex is a heteropentameric protein unit associated with retrograde transport of cargo proteins from endosomes to the trans-Golgi network. Functional silencing study of the Vps26a gene indicated the important role of the retromer complex during early developmental stages in the mouse. However, individual expression patterns and quantitative analysis of individual members of the retromer complex during the early developmental stages has not been investigated. In this study, we conducted quantitative expression analysis of six retromer complex genes (Vps26a, Vps26b, Vps29, Vps35, Snx1, and Snx2) and one related receptor gene (Ci-mpr) during the eleven embryonic stages with normal MEF (mouse embryonic fibroblast) and Vps26a(-/-) MEF cells...
May 2011: Molecules and Cells
#35
JOURNAL ARTICLE
Ekyune Kim, Youngjeon Lee, Hyun-Ju Lee, Ji Su Kim, Bong-Seok Song, Jae-Won Huh, Sang-Rae Lee, Sun-Uk Kim, Sang-Hyun Kim, Yonggeun Hong, Insop Shim, Kyu-Tae Chang
The retromer complex, which mediates retrograde transport from endosomes to the trans-Golgi network, is a heteropentameric complex that contains a multifunctional cargo recognition heterotrimer consisted of the vacuolar protein sorting (Vps) subunits Vps26, Vps29, and Vps35. In mammals, there are two different isoforms of Vps26, Vps26a and Vps26b, that localize to the endosome, and to the plasma membrane, respectively. To elucidate the biological significance of the Vps26b isoform, we generated Vps26b knockout mice and studied their molecular, histological, and behavioral phenotypes...
December 10, 2010: Biochemical and Biophysical Research Communications
#36
JOURNAL ARTICLE
Emélie Braschi, Vanessa Goyon, Rodolfo Zunino, Abhishek Mohanty, Liqun Xu, Heidi M McBride
Mitochondria-derived vesicles (MDVs) have been shown to transport cargo from the mitochondria to the peroxisomes. Mitochondria and peroxisomes share common functions in the oxidation of fatty acids and the reduction of damaging peroxides. Their biogenesis is also linked through both the activation of master transcription factors such as PGC-1alpha and the common use of fission machinery, including DRP1, Mff, and hFis1. We have previously shown that MDVs are formed independently of the known mitochondrial fission GTPase Drp1 and are enriched for a mitochondrial small ubiquitin-like modifier (SUMO) E3 ligase called MAPL (mitochondrial-anchored protein ligase)...
July 27, 2010: Current Biology: CB
#37
JOURNAL ARTICLE
Ekyune Kim, Jae-Woong Lee, Dong-Chul Baek, Sang-Rae Lee, Myeong-Su Kim, Sang-Hyun Kim, Kazuhiko Imakawa, Kyu-Tae Chang
A family of vacuolar protein sorting (Vps) proteins, which are components of mammalian retromer complex, has been studied in the mouse. Vps26a is known as a retromer component that plays an important role in embryonic development: however, its cell-type expression and precise role remain to be elucidated. In this study, we identified a new isoform of Vps26a, called Vps26aT, which was expressed specifically in the mouse testis. Diverse expression patterns of Vps26 variants in mouse tissues were determined by Western blot and RT-PCR analyses, and the direct interaction of Vps26aT with Vps35 was also demonstrated by immunoprecipitation and pull-down assay using antibodies raised against each Vps component...
October 10, 2008: Biochemical and Biophysical Research Communications
#38
COMPARATIVE STUDY
Brett M Collins, Suzanne J Norwood, Markus C Kerr, Donna Mahony, Matthew N J Seaman, Rohan D Teasdale, David J Owen
Retromer is a heteromeric protein complex with important roles in endosomal membrane trafficking, most notably in the retrograde transport of lysosomal hydrolase receptors from endosomes to the Golgi. The core of retromer is composed of three subunits vacuolar protein sorting (Vps)35, Vps26 and Vps29, and in mammals, there are two paralogues of the medium subunit Vps26A and Vps26B. We find that both Vps26A and Vps26B bind to Vps35/Vps29 with nanomolar affinity and compete for a single-binding site to define distinct retromer complexes in vitro and in vivo...
March 2008: Traffic
#39
JOURNAL ARTICLE
Hang Shi, Raul Rojas, Juan S Bonifacino, James H Hurley
The mammalian retromer complex consists of SNX1, SNX2, Vps26, Vps29 and Vps35, and retrieves lysosomal enzyme receptors from endosomes to the trans-Golgi network. The structure of human Vps26A at 2.1-A resolution reveals two curved beta-sandwich domains connected by a polar core and a flexible linker. Vps26 has an unpredicted structural relationship to arrestins. The Vps35-binding site on Vps26 maps to a mobile loop spanning residues 235-246, near the tip of the C-terminal domain. The loop is phylogenetically conserved and provides a mechanism for Vps26 integration into the complex that leaves the rest of the structure free for engagements with membranes and for conformational changes...
June 2006: Nature Structural & Molecular Biology
#40
JOURNAL ARTICLE
Markus C Kerr, Jennifer S Bennetts, Fiona Simpson, Elaine C Thomas, Cameron Flegg, Paul A Gleeson, Carol Wicking, Rohan D Teasdale
The mammalian retromer protein complex, which consists of three proteins--Vps26, Vps29, and Vps35--in association with members of the sorting nexin family of proteins, has been implicated in the trafficking of receptors and their ligands within the endosomal/lysosomal system of mammalian cells. A bioinformatic analysis of the mouse genome identified an additional transcribed paralog of the Vps26 retromer protein, which we termed Vps26B. No paralogs were identified for Vps29 and Vps35. Phylogenetic studies indicate that the two paralogs of Vps26 become evident after the evolution of the chordates...
November 2005: Traffic
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