keyword
MENU ▼
Read by QxMD icon Read
search

Retromer

keyword
https://www.readbyqxmd.com/read/28442266/cln5-is-cleaved-by-members-of-the-spp-sppl-family-to-produce-a-mature-soluble-protein
#1
Felix Jules, Etienne Sauvageau, Karine Dumaresq-Doiron, Javier Mazzaferri, Martina Haug-Kröper, Regina Fluhrer, Santiago Costantino, Stephane Lefrancois
The Neuronal ceroid lipofuscinoses (NCLs) are a group of recessive disorders of childhood with overlapping symptoms including vision loss, ataxia, cognitive regression and premature death. 14 different genes have been linked to NCLs (CLN1-CLN14), but the functions of the proteins encoded by the majority of these genes have not been fully elucidated. Mutations in the CLN5 gene are responsible for the Finnish variant late-infantile form of NCL (Finnish vLINCL). CLN5 is translated as a 407 amino acid transmembrane domain containing protein that is heavily glycosylated, and subsequently cleaved into a mature soluble protein...
April 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28399880/quantitative-proteomic-analysis-of-parkin-substrates-in-drosophila-neurons
#2
Aitor Martinez, Benoit Lectez, Juanma Ramirez, Oliver Popp, James D Sutherland, Sylvie Urbé, Gunnar Dittmar, Michael J Clague, Ugo Mayor
BACKGROUND: Parkin (PARK2) is an E3 ubiquitin ligase that is commonly mutated in Familial Parkinson's Disease (PD). In cell culture models, Parkin is recruited to acutely depolarised mitochondria by PINK1. PINK1 activates Parkin activity leading to ubiquitination of multiple proteins, which in turn promotes clearance of mitochondria by mitophagy. Many substrates have been identified using cell culture models in combination with depolarising drugs or proteasome inhibitors, but not in more physiological settings...
April 11, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28399507/the-emerging-role-of-retromer-in-neuroprotection
#3
REVIEW
Kirsty J McMillan, Hendrick C Korswagen, Peter J Cullen
Efficient sorting and transportation of integral membrane proteins, such as ion channels, nutrient transporters, signalling receptors, cell-cell and cell-matrix adhesion molecules is essential for the function of cellular organelles and hence organism development and physiology. Retromer is a master controller of integral membrane protein sorting and transport through one of the major sorting station within eukaryotic cells, the endosomal network. Subtle de-regulation of retromer is an emerging theme in the pathoetiology of Parkinson's disease...
April 8, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28384478/the-retromer-supports-ampa-receptor-trafficking-during-ltp
#4
Paul Temkin, Wade Morishita, Debanjan Goswami, Kristin Arendt, Lu Chen, Robert Malenka
Alterations in the function of the retromer, a multisubunit protein complex that plays a specialized role in endosomal sorting, have been linked to Alzheimer's and Parkinson's diseases, yet little is known about the retromer's role in the mature brain. Using in vivo knockdown of the critical retromer component VPS35, we demonstrate a specific role for this endosomal sorting complex in the trafficking of AMPA receptors during NMDA-receptor-dependent LTP at mature hippocampal synapses. The impairment of LTP due to VPS35 knockdown was mechanistically independent of any role of the retromer in the production of Aβ from APP...
April 5, 2017: Neuron
https://www.readbyqxmd.com/read/28362258/a-cdc25-family-protein-phosphatase-gates-cargo-recognition-by-the-vps26-retromer-subunit
#5
Tie-Zhong Cui, Tabitha A Peterson, Christopher G Burd
We describe a regulatory mechanism that controls the activity of retromer, an evolutionarily conserved sorting device that orchestrates cargo export from the endosome. A spontaneously arising mutation that activates the yeast (Saccharomyces cerevisiae) CDC25 family phosphatase, Mih1, results in accelerated turnover of a subset of endocytosed plasma membrane proteins due to deficient sorting into a retromer-mediated recycling pathway. Mih1 directly modulates the phosphorylation state of the Vps26 retromer subunit; mutations engineered to mimic these states modulate the binding affinities of Vps26 for a retromer cargo, resulting in corresponding changes in cargo sorting at the endosome...
March 31, 2017: ELife
https://www.readbyqxmd.com/read/28353286/interaction-of-lrrk2-and-%C3%AE-synuclein-in-parkinson-s-disease
#6
João Paulo Lima Daher
Parkinson's disease (PD) is a progressively debilitating neurodegenerative syndrome. It is best described as a movement disorder characterized by motor dysfunctions, progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta, and abnormal intraneuronal protein aggregates, named Lewy bodies and Lewy neurites. Nevertheless, knowledge of the molecular events leading to this pathophysiology is incomplete. To date, only mutations in the α-synuclein and LRRK2-encoding genes have been associated with typical findings of clinical and pathologic PD...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28252385/chlamydia-interfere-with-an-interaction-between-the-mannose-6-phosphate-receptor-and-sorting-nexins-to-counteract-host-restriction
#7
Cherilyn A Elwell, Nadine Czudnochowski, John von Dollen, Jeffrey R Johnson, Rachel Nakagawa, Kathleen Mirrashidi, Nevan J Krogan, Joanne N Engel, Oren S Rosenberg
Chlamydia trachomatis is an obligate intracellular pathogen that resides in a membrane-bound compartment, the inclusion. The bacteria secrete a unique class of proteins, Incs, which insert into the inclusion membrane and modulate the host-bacterium interface. We previously reported that IncE binds specifically to the Sorting Nexin 5 Phox domain (SNX5-PX) and disrupts retromer trafficking. Here, we present the crystal structure of the SNX5-PX:IncE complex, showing IncE bound to a unique and highly conserved hydrophobic groove on SNX5...
March 2, 2017: ELife
https://www.readbyqxmd.com/read/28222538/vps35-the-retromer-complex-and-parkinson-s-disease
#8
Erin T Williams, Xi Chen, Darren J Moore
Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene encoding a core component of the retromer complex, have recently emerged as a new cause of late-onset, autosomal dominant familial Parkinson's disease (PD). A single missense mutation, AspD620Asn (D620N), has so far been unambiguously identified to cause PD in multiple individuals and families worldwide. The exact molecular mechanism(s) by which VPS35 mutations induce progressive neurodegeneration in PD are not yet known. Understanding these mechanisms, as well as the perturbed cellular pathways downstream of mutant VPS35, is important for the development of appropriate therapeutic strategies...
February 8, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28179995/caspase-mediated-proteolysis-of-the-sorting-nexin-2-disrupts-retromer-assembly-and-potentiates-met-hepatocyte-growth-factor-receptor-signaling
#9
Catherine M Duclos, Audrey Champagne, Julie C Carrier, Caroline Saucier, Christine L Lavoie, Jean-Bernard Denault
The unfolding of apoptosis involves the cleavage of hundreds of proteins by the caspase family of cysteinyl peptidases. Among those substrates are proteins involved in intracellular vesicle trafficking with a net outcome of shutting down the crucial processes governing protein transport to organelles and to the plasma membrane. However, because of the intertwining of receptor trafficking and signaling, cleavage of specific proteins may lead to unintended consequences. Here we show that in apoptosis, sorting nexin 1 and 2 (SNX1 and SNX2), two proteins involved in endosomal sorting, are cleaved by initiator caspases and also by executioner caspase-6 in the case of SNX2...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28134614/ablation-of-snx6-leads-to-defects-in-synaptic-function-of-ca1-pyramidal-neurons-and-spatial-memory
#10
Yang Niu, Zhonghua Dai, Wenxue Liu, Cheng Zhang, Yanrui Yang, Zhenzhen Guo, Xiaoyu Li, Chenchang Xu, Xiahe Huang, Yingchun Wang, Yun S Shi, Jia-Jia Liu
SNX6 is a ubiquitously expressed PX-BAR protein that plays important roles in retromer-mediated retrograde vesicular transport from endosomes. Here we report that CNS-specific Snx6 knockout mice exhibit deficits in spatial learning and memory, accompanied with loss of spines from distal dendrites of hippocampal CA1 pyramidal cells. SNX6 interacts with Homer1b/c, a postsynaptic scaffold protein crucial for the synaptic distribution of other postsynaptic density (PSD) proteins and structural integrity of dendritic spines...
January 30, 2017: ELife
https://www.readbyqxmd.com/read/28131823/in-situ-peroxidase-labeling-and-mass-spectrometry-connects-alpha-synuclein-directly-to-endocytic-trafficking-and-mrna-metabolism-in-neurons
#11
Chee Yeun Chung, Vikram Khurana, Song Yi, Nidhi Sahni, Ken H Loh, Pavan K Auluck, Valeriya Baru, Namrata D Udeshi, Yelena Freyzon, Steven A Carr, David E Hill, Marc Vidal, Alice Y Ting, Susan Lindquist
Synucleinopathies, including Parkinson's disease (PD), are associated with the misfolding and mistrafficking of alpha-synuclein (α-syn). Here, using an ascorbate peroxidase (APEX)-based labeling method combined with mass spectrometry, we defined a network of proteins in the immediate vicinity of α-syn in living neurons to shed light on α-syn function. This approach identified 225 proteins, including synaptic proteins, proteins involved in endocytic vesicle trafficking, the retromer complex, phosphatases and mRNA binding proteins...
February 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28129035/where-no-ras-has-gone-before-vps35-steers-n-ras-through-the-cytosol
#12
Mo Zhou, Mark R Philips
Ras is the best-studied member of the superfamily of small GTPases because of its role in cancer. Ras proteins transmit signals for proliferation, differentiation and survival. Three RAS genes encode 4 isoforms. All Ras isoforms have long been considered membrane bound, a localization required for function. Our recent study revealed that N-Ras differs from all other isoforms in being largely cytosolic even following modification with a prenyl lipid. Endogenous, cytosolic N-Ras chromatographed in both high and low molecular weight pools, a pattern that required prenylation, suggesting prenyl-dependent interaction with other proteins...
January 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28115417/the-parkinson-s-disease-linked-protein-tmem230-is-required-for-rab8a-mediated-secretory-vesicle-trafficking-and-retromer-trafficking
#13
Myung Jong Kim, Han-Xiang Deng, Yvette C Wong, Teepu Siddique, Dimitri Krainc
TMEM230 is a newly identified Parkinson's disease (PD) gene encoding a transmembrane protein whose cellular and pathogenic roles remain largely unknown. Here, we demonstrate that loss of TMEM230 disrupts retromer cargo CI-M6PR (cation-independent mannose 6-phosphate receptor) trafficking and autophagic cargo degradation rates. TMEM230 depletion further inhibits extracellular secretion of the autophagic cargo p62 and immature lysosomal hydrolases in Golgi-derived vesicles leading to their intracellular accumulation, and is specifically mediated by loss of the small GTPase Rab8a...
February 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28110103/the-retromer-complex-system-in-a-transgenic-mouse-model-of-ad-influence-of-age
#14
Jin Chu, Domenico Praticò
Deficiencies of the retrograde transport mediated by the retromer complex have been described in Alzheimer's disease (AD). Genetic manipulation of retromer modulates brain amyloidosis in Tg2576 mice. However, whether the complex is altered during the development of the AD-like phenotype remains unknown. In this study we assayed the expression levels of the vacuolar sorting protein 35 (VPS35), VPS26, VPS29, and its cargo proteins, cation independent mannose 6-phosphate receptor, sortilin-related receptor in brains of Tg2576 and controls at the ages of 3, 8, and 14 months...
January 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28100638/retromer-driven-membrane-tubulation-separates-endosomal-recycling-from-rab7-ypt7-dependent-fusion
#15
Latha Kallur Purushothaman, Henning Arlt, Anne Kuhlee, Stefan Raunser, Christian Ungermann
Endosomes are the major protein-sorting hubs of the endocytic pathway. They sort proteins destined for degradation into internal vesicles while in parallel recycling receptors via tubular carriers back to the Golgi. Tubule formation depends on the Rab7/Ypt7-interacting retromer complex, consisting of the sorting nexin dimer (SNX-BAR) and the trimeric cargo selection complex (CSC). Fusion of mature endosomes with the lysosome-like vacuole also requires Rab7/Ypt7. Here we solve a major problem in understanding this dual function of endosomal Rab7/Ypt7, using a fully reconstituted system, including purified, full-length yeast SNX-BAR and CSC, whose overall structure we present...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28053230/snx-1-and-rme-8-oppose-the-assembly-of-hgrs-1-escrt-0-degradative-microdomains-on-endosomes
#16
Anne Norris, Prasad Tammineni, Simon Wang, Julianne Gerdes, Alexandra Murr, Kelvin Y Kwan, Qian Cai, Barth D Grant
After endocytosis, transmembrane cargo reaches endosomes, where it encounters complexes dedicated to opposing functions: recycling and degradation. Microdomains containing endosomal sorting complexes required for transport (ESCRT)-0 component Hrs [hepatocyte growth factor-regulated tyrosine kinase substrate (HGRS-1) in Caenorhabditis elegans] mediate cargo degradation, concentrating ubiquitinated cargo and organizing the activities of ESCRT. At the same time, retromer associated sorting nexin one (SNX-1) and its binding partner, J-domain protein RME-8, sort cargo away from degradation, promoting cargo recycling to the Golgi...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28040727/a-conserved-retromer-sorting-motif-is-essential-for-mitochondrial-dlp1-recycling-by-vps35-in-parkinson-s-disease-model
#17
Wenzhang Wang, Xiaopin Ma, Leping Zhou, Jun Liu, Xiongwei Zhu
Impaired mitochondria dynamics and quality control are involved in mitochondrial dysfunction and pathogenesis of Parkinson's disease (PD). VPS35 mutations cause autosomal dominant PD and we recently demonstrated that fPD-associated VPS35 mutants can cause mitochondrial fragmentation through enhanced VPS35-DLP1 interaction. In this study, we focused on the specific sites on DLP1 responsible for the VPS35-DLP1 interaction. A highly conserved FLV motif was identified in the C-terminus of DLP1, mutation of which significantly reduced VPS35-DLP1 interaction...
February 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28026081/distinct-complexes-of-yeast-snx4-family-snx-bars-mediate-retrograde-trafficking-of-snc1-and-atg27
#18
Mengxiao Ma, Christopher G Burd, Richard J Chi
The yeast SNX4 sub-family of sorting nexin containing a Bin-Amphiphysin-Rvs domain (SNX-BAR) proteins, Snx4/Atg24, Snx41 and Atg20/Snx42, are required for endocytic recycling and selective autophagy. Here, we show that Snx4 forms 2 functionally distinct heterodimers: Snx4-Atg20 and Snx4-Snx41. Each heterodimer coats an endosome-derived tubule that mediates retrograde sorting of distinct cargo; the v-SNARE, Snc1, is a cargo of the Snx4-Atg20 pathway, and Snx4-Snx41 mediates retrograde sorting of Atg27, an integral membrane protein implicated in selective autophagy...
February 2017: Traffic
https://www.readbyqxmd.com/read/27984059/cruising-the-cellular-highways-how-human-papillomavirus-travels-from-the-surface-to-the-nucleus
#19
REVIEW
Stephen DiGiuseppe, Malgorzata Bienkowska-Haba, Lucile G Guion, Martin Sapp
The non-enveloped human papillomaviruses (HPVs) specifically target epithelial cells of the skin and mucosa. Successful infection requires a lesion in the stratified tissue for access to the basal cells. Herein, we discuss our recent progress in understanding binding, internalization, uncoating, and intracellular trafficking of HPV particles. Our focus will be on HPV type 16, which is the most common HPV type associated with various anogenital and oropharyngeal carcinomas. The study of HPV entry has revealed a number of novel cellular pathways utilized during infection...
March 2, 2017: Virus Research
https://www.readbyqxmd.com/read/27964832/role-of-the-vps35-d620n-mutation-in-parkinson-s-disease
#20
REVIEW
Megha Mohan, George D Mellick
Parkinson's disease (PD) is a neurodegenerative disorder involving the loss of dopaminergic neurons in the brain. Following the discovery of the PD-causing D620N mutation in the VPS35 (Vacuolar sorting protein 35) gene, dysfunction in the subcellular retromer complex has been strongly implicated in pathogenesis of PD. Although the function and dysfunction of the retromer has been a focus of study for some time, the role of this complex in the development of PD is not fully understood. Investigating cellular alterations that occur when the retromer is rendered dysfunctional, such as when the D620N disease-causing mutation is introduced into various model systems, shows that endosomal processing defects are major contributors to the disease phenotype...
March 2017: Parkinsonism & related Disorders
keyword
keyword
68265
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"