scholarly journals Rapid Endosomal Recycling

2018 ◽  
Author(s):  
Hana Mahmutefendić ◽  
Gordana Blagojević Zagorac ◽  
Senka Maćešić ◽  
Pero Lučin
Keyword(s):  
Endosomal Recycling

scholarly journals The Arabidopsis GNOM ARF-GEF Mediates Endosomal Recycling, Auxin Transport, and Auxin-Dependent Plant Growth

Cell ◽  
2003 ◽  
Vol 112 (2) ◽  
pp. 219-230 ◽  
Author(s):  
Niko Geldner ◽  
Nadine Anders ◽  
Hanno Wolters ◽  
Jutta Keicher ◽  
Wolfgang Kornberger ◽  
...  
Keyword(s):  
Plant Growth ◽  
Auxin Transport ◽  
Endosomal Recycling

scholarly journals The Alzheimer's gene SORL1 is a key regulator of endosomal recycling in human neurons

2021 ◽  
Author(s):  
Swati Mishra ◽  
Allison Knupp ◽  
Marcell Szabo ◽  
Chizuru Kinoshita ◽  
Dale W. Hailey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Induced Pluripotent Stem Cell ◽  
Endosomal Trafficking ◽  
Altered Expression ◽  
Therapeutic Implications ◽  
Endosomal Recycling ◽  
Human Neurons ◽  
Early Endosomes

Background: Loss of the Sortilin-related receptor 1 (SORL1) gene seems to act as a causal event for Alzheimer's disease (AD). Recent studies have established that loss of SORL1, as well as mutations in autosomal dominant AD genes APP and PSEN1/2, pathogenically converge by swelling early endosomes, AD's cytopathological hallmark. Acting together with the retromer trafficking complex, SORL1 has been shown to regulate the recycling of the amyloid precursor protein (APP) out of the endosome, contributing to endosomal swelling and to APP misprocessing. We hypothesized that SORL1 plays a broader role in neuronal endosomal recycling and used human induced pluripotent stem cell derived neurons (hiPSC-Ns) to test this hypothesis. We examined endosomal recycling of three transmembrane proteins linked to AD pathophysiology: APP, the BDNF receptor Tropomyosin-related kinase B (TRKB), and the glutamate receptor subunit AMPA1 (GLUA1). Methods: We used isogenic hiPSCs engineered to have SORL1 depleted or to have enhanced SORL1 expression. We differentiated neurons from these cell lines and mapped the trafficking of APP, TRKB and GLUA1 within the endosomal network using confocal microscopy. We also performed cell surface recycling and lysosomal degradation assays to assess the functionality of the endosomal network. Finally, we analyzed alterations in gene expression in SORL1 depleted neurons using RNA-sequencing. Results: We find that as with APP, endosomal trafficking of GLUA1 and TRKB is impaired by loss of SORL1. Conversely, increased SORL1 expression enhances endosomal recycling for APP and GLUA1. Our unbiased transcriptomic data further support SORL1's role in endosomal recycling. We observe altered expression networks that regulate cell surface trafficking and neurotrophic signaling Conclusion: Collectively, and together with other recent observations, these findings suggest that SORL1 is a key and broad regulator of retromer-dependent endosomal recycling in neurons, a conclusion that has both pathogenic and therapeutic implications for Alzheimer's disease.

scholarly journals RABENOSYN separation-of-function mutations uncouple endosomal recycling from lysosomal degradation

2021 ◽  
Author(s):  
Franziska Paul ◽  
Calista Ng ◽  
Shahriar Nafissi ◽  
Yalda Nilipoor ◽  
Ali Reza Tavasoli ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Exome Sequencing ◽  
Muscle Weakness ◽  
Germline Mutations ◽  
Lysosomal Degradation ◽  
Mendelian Disorder ◽  
Progressive Muscle Weakness ◽  
Endosomal Recycling ◽  
Early Endosomes ◽  
Recycling Pathway

Rabenosyn (RBSN) is a conserved endosomal protein necessary for regulating internalized cargo. Here, we present genetic, cellular and biochemical evidence that two distinct RBSN missense variants are responsible for a novel Mendelian disorder consisting of progressive muscle weakness, facial dysmorphisms, ophthalmoplegia and intellectual disability. Using exome sequencing, we identified recessively-acting germline alleles p.Arg180Gly and p.Gly183Arg which are both situated in the FYVE domain of RBSN. We find that these variants abrogate binding to its cognate substrate PI3P and thus prevent its translocation to early endosomes. Although the endosomal recycling pathway was unaltered, mutant p.Gly183Arg patient fibroblasts exhibit accumulation of cargo tagged for lysosomal degradation. Our results suggest that these variants are separation-of-function alleles, which cause a delay in endosomal maturation without affecting cargo recycling. We conclude that distinct germline mutations in RBSN cause non-overlapping phenotypes with specific and discrete endolysosomal cellular defects.

scholarly journals TFEB controls retromer expression in response to nutrient availability

2019 ◽  
Vol 218 (12) ◽  
pp. 3954-3966 ◽  
Author(s):  
Rachel Curnock ◽  
Alessia Calcagni ◽  
Andrea Ballabio ◽  
Peter J. Cullen
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Amino Acid ◽  
Cell Surface ◽  
Nutrient Uptake ◽  
Nutrient Availability ◽  
Amino Acid Starvation ◽  
Endosomal Recycling ◽  
Transcription Factor Eb ◽  
Glutamine Transporters

Endosomal recycling maintains the cell surface abundance of nutrient transporters for nutrient uptake, but how the cell integrates nutrient availability with recycling is less well understood. Here, in studying the recycling of human glutamine transporters ASCT2 (SLC1A5), LAT1 (SLC7A5), SNAT1 (SLC38A1), and SNAT2 (SLC38A2), we establish that following amino acid restriction, the adaptive delivery of SNAT2 to the cell surface relies on retromer, a master conductor of endosomal recycling. Upon complete amino acid starvation or selective glutamine depletion, we establish that retromer expression is upregulated by transcription factor EB (TFEB) and other members of the MiTF/TFE family of transcription factors through association with CLEAR elements in the promoters of the retromer genes VPS35 and VPS26A. TFEB regulation of retromer expression therefore supports adaptive nutrient acquisition through endosomal recycling.

scholarly journals VPS29, a tweak tool of endosomal recycling

2019 ◽  
Vol 59 ◽  
pp. 81-87 ◽  
Author(s):  
Soledad Baños-Mateos ◽  
Adriana L Rojas ◽  
Aitor Hierro
Keyword(s):  
Endosomal Recycling

scholarly journals The U24 Protein from Human Herpesvirus 6 and 7 Affects Endocytic Recycling

2009 ◽  
Vol 84 (3) ◽  
pp. 1265-1275 ◽  
Author(s):  
Brian M. Sullivan ◽  
Laurent Coscoy
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Human Herpesvirus ◽  
Cell Receptor ◽  
Receptor Expression ◽  
Membrane Insertion ◽  
Human Herpesvirus 6 ◽  
Endosomal Recycling ◽  
Endosomal Transport ◽  
Basic Cellular Process

ABSTRACT Modulation of T-cell receptor expression and signaling is essential to the survival of many viruses. The U24 protein expressed by human herpesvirus 6A, a ubiquitous human pathogen, has been previously shown to downregulate the T-cell receptor. Here, we show that U24 also mediates cell surface downregulation of a canonical early endosomal recycling receptor, the transferrin receptor, indicating that this viral protein acts by blocking early endosomal recycling. We present evidence that U24 is a C-tail-anchored protein that is dependent for its function on TRC40/Asna-1, a component of a posttranslational membrane insertion pathway. Finally, we find that U24 proteins from other roseoloviruses have a similar genetic organization and a conserved function that is dependent on a proline-rich motif. Inhibition of a basic cellular process by U24 has interesting implications not only for the pathogenicity of roseoloviruses but also for our understanding of the biology of endosomal transport.

RAB14 and RAB5 Gtpases Regulate Human Erythropoiesis, Potentially Via Opposing Roles in Endosomal Recycling

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 937-937
Author(s):  
MinJung Kim ◽  
Tami J. Kingsbury ◽  
Wen-Chih Cheng ◽  
Yee Sun Tan ◽  
Brittany M. Taylor ◽  
...  
Keyword(s):  
Cell Surface ◽  
Conflicts Of Interest ◽  
Degradation Pathway ◽  
Rab Gtpases ◽  
Recycling Endosome ◽  
Hematopoietic Stem ◽  
Surface Receptors ◽  
Protein Levels ◽  
Endosomal Recycling ◽  
Model Cell

Abstract Previously, we reported that the erythroid-expressed miRs, miR-144 and miR-451, target the RAB14 GTPase during human erythropoiesis in the human TF1 erythropoietic model cell line and in primary CD34+ hematopoietic stem-progenitor cells. In response to erythropoietin, endogenous RAB14 levels decreased during erythropoiesis, and RAB14 knockdown increased the numbers of erythroid (CD34- CD71hi CD235ahi) cells, increased b-hemoglobin expression, and decreased ETO2 expression (Kim, BJH, 2015). Taken together, our findings revealed that RAB14 functions as a physiologic inhibitor of human erythropoiesis. RAB GTPases comprise a >60 member subfamily of the large RAS oncogene family, and multiple RAB GTPases play important roles in vesicle trafficking, signal transduction and receptor recycling. RAB14 is a component of the intermediate compartment of the endosomal recycling pathway, between the RAB4/RAB5-dependent early endosome and the RAB11-dependent recycling endosome (Linford, Dev. Cell, 2012). The RAB GTPases are responsible for directing cargo proteins to the recycling vs. degradation pathway during endosome maturation. To test the role of another endosomal RAB GTPases in human erythropoiesis, we examined the consequences of knocking down RAB5 protein levels. In contrast to our findings with RAB14, knockdown of RAB5C decreased the numbers of erythroid cells generated during erythropoiesis, indicating that RAB5C enhances physiologic erythropoiesis. Consistent with this observation, mRNA and protein levels for all three RAB5 isoforms (i.e. RAB5A, B, C) increased during erythropoiesis. The opposing erythropoietic effects of RAB14 and RAB5 GTPases may be due to their contrary roles in endosomal recycling, in that internalization of cell surface receptors is dependent on RAB5 GTPase, whereas RAB14 GTPase is involved in recycling of receptors back to the cell surface. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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