TrafficPub Date : 2023-12-01Epub Date: 2023-09-02DOI: 10.1111/tra.12918
Chenyao Wang, Nikhil Sharma, Patricia M Kessler, Ganes C Sen
{"title":"Interferon induction by STING requires its translocation to the late endosomes.","authors":"Chenyao Wang, Nikhil Sharma, Patricia M Kessler, Ganes C Sen","doi":"10.1111/tra.12918","DOIUrl":"10.1111/tra.12918","url":null,"abstract":"<p><p>To combat microbial infections, mammalian cells use a variety of innate immune response pathways to induce synthesis of anti-microbial proteins. The cGAS/STING pathway recognizes cytoplasmic viral or cellular DNA to elicit signals that lead to type I interferon and other cytokine synthesis. cGAMP, synthesized by DNA-activated cGAS, activates the ER-associated protein, STING, which oligomerizes and translocates to other intracellular membrane compartments to trigger different branches of signaling. We have reported that, in the ER, EGFR-mediated phosphorylation of Tyr245 of STING is required for its transit to the late endosomes, where it recruits and activates the transcription factor IRF3 required for IFN induction. In the current study, we inquired whether STING Tyr245 phosphorylation per se or STING's location in the late endosomes was critical for its ability to recruit IRF3 and induce IFN. Using pharmacological inhibitors or genetic ablation of proteins that are essential for specific steps of STING trafficking, we demonstrated that the presence of STING in the late endosomal membranes, even without Tyr245 phosphorylation, was sufficient for IRF3-mediated IFN induction.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":" ","pages":"576-586"},"PeriodicalIF":3.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10201531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-11-01Epub Date: 2023-08-06DOI: 10.1111/tra.12913
Hyerim Ahn, Xavier Durang, Jae Youn Shim, Gaeun Park, Jae-Hyung Jeon, Hye Yoon Park
{"title":"Statistical modeling of mRNP transport in dendrites: A comparative analysis of β-actin and Arc mRNP dynamics.","authors":"Hyerim Ahn, Xavier Durang, Jae Youn Shim, Gaeun Park, Jae-Hyung Jeon, Hye Yoon Park","doi":"10.1111/tra.12913","DOIUrl":"10.1111/tra.12913","url":null,"abstract":"<p><p>Localization of messenger RNA (mRNA) in dendrites is crucial for regulating gene expression during long-term memory formation. mRNA binds to RNA-binding proteins (RBPs) to form messenger ribonucleoprotein (mRNP) complexes that are transported by motor proteins along microtubules to their target synapses. However, the dynamics by which mRNPs find their target locations in the dendrite have not been well understood. Here, we investigated the motion of endogenous β-actin and Arc mRNPs in dissociated mouse hippocampal neurons using the MS2 and PP7 stem-loop systems, respectively. By evaluating the statistical properties of mRNP movement, we found that the aging Lévy walk model effectively describes both β-actin and Arc mRNP transport in proximal dendrites. A critical difference between β-actin and Arc mRNPs was the aging time, the time lag between transport initiation and measurement initiation. The longer mean aging time of β-actin mRNP (~100 s) compared with that of Arc mRNP (~30 s) reflects the longer half-life of constitutively expressed β-actin mRNP. Furthermore, our model also permitted us to estimate the ratio of newly generated and pre-existing β-actin mRNPs in the dendrites. This study offers a robust theoretical framework for mRNP transport, which provides insight into how mRNPs locate their targets in neurons.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":" ","pages":"522-532"},"PeriodicalIF":4.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10319298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-11-01Epub Date: 2023-07-26DOI: 10.1111/tra.12912
Julia E J Holm, Sandro G Soares, Martyn F Symmons, Afiqah Saleh Huddin, Martin C Moncrieffe, Nicholas J Gay
{"title":"Anterograde trafficking of Toll-like receptors requires the cargo sorting adaptors TMED-2 and 7.","authors":"Julia E J Holm, Sandro G Soares, Martyn F Symmons, Afiqah Saleh Huddin, Martin C Moncrieffe, Nicholas J Gay","doi":"10.1111/tra.12912","DOIUrl":"10.1111/tra.12912","url":null,"abstract":"<p><p>Toll-Like Receptors (TLRs) play a pivotal role in immunity by recognising conserved structural features of pathogens and initiating the innate immune response. TLR signalling is subject to complex regulation that remains poorly understood. Here we show that two small type I transmembrane receptors, TMED2 and 7, that function as cargo sorting adaptors in the early secretory pathway are required for transport of TLRs from the ER to Golgi. Protein interaction studies reveal that TMED7 interacts with TLR2, TLR4 and TLR5 but not with TLR3 and TLR9. On the other hand, TMED2 interacts with TLR2, TLR4 and TLR3. Dominant negative forms of TMED7 suppress the export of cell surface TLRs from the ER to the Golgi. By contrast TMED2 is required for the ER-export of both plasma membrane and endosomal TLRs. Together, these findings suggest that association of TMED2 and TMED7 with TLRs facilitates anterograde transport from the ER to the Golgi.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":" ","pages":"508-521"},"PeriodicalIF":4.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-11-01Epub Date: 2023-08-14DOI: 10.1111/tra.12915
Anja J Engel, Steffen Paech, Markus Langhans, James L van Etten, Anna Moroni, Gerhard Thiel, Oliver Rauh
{"title":"Combination of hydrophobicity and codon usage bias determines sorting of model K<sup>+</sup> channel protein to either mitochondria or endoplasmic reticulum.","authors":"Anja J Engel, Steffen Paech, Markus Langhans, James L van Etten, Anna Moroni, Gerhard Thiel, Oliver Rauh","doi":"10.1111/tra.12915","DOIUrl":"10.1111/tra.12915","url":null,"abstract":"<p><p>When the K<sup>+</sup> channel-like protein Kesv from Ectocarpus siliculosus virus 1 is heterologously expressed in mammalian cells, it is sorted to the mitochondria. This targeting can be redirected to the endoplasmic reticulum (ER) by altering the codon usage in distinct regions of the gene or by inserting a triplet of hydrophobic amino acids (AAs) into the protein's C-terminal transmembrane domain (ct-TMD). Systematic variations in the flavor of the inserted AAs and/or its codon usage show that a positive charge in the inserted AA triplet alone serves as strong signal for mitochondria sorting. In cases of neutral AA triplets, mitochondria sorting are favored by a combination of hydrophilic AAs and rarely used codons; sorting to the ER exhibits the inverse dependency. This propensity for ER sorting is particularly high when a common codon follows a rarer one in the AA triplet; mitochondria sorting in contrast is supported by codon uniformity. Since parameters like positive charge, hydrophobic AAs, and common codons are known to facilitate elongation of nascent proteins in the ribosome the data suggest a mechanism in which local changes in elongation velocity and co-translational folding in the ct-TMD influence intracellular protein sorting.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":" ","pages":"533-545"},"PeriodicalIF":4.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10362730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-11-01Epub Date: 2023-08-15DOI: 10.1111/tra.12914
Eric Chevet, Maria Antonietta De Matteis, Eeva-Liisa Eskelinen, Hesso Farhan
{"title":"Dynamic tandem proximity-based proteomics-Protein trafficking at the proteome-scale.","authors":"Eric Chevet, Maria Antonietta De Matteis, Eeva-Liisa Eskelinen, Hesso Farhan","doi":"10.1111/tra.12914","DOIUrl":"10.1111/tra.12914","url":null,"abstract":"<p><p>TransitID is a new methodology based on proximity labeling allowing for the study of protein trafficking a the proteome scale.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":" ","pages":"546-548"},"PeriodicalIF":4.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-09-01DOI: 10.1111/tra.12905
Zhiwei Liao, Bide Tong, Zixuan Ou, Junyu Wei, Ming Lei, Cao Yang
{"title":"The role of extracellular vesicles in iron homeostasis and ferroptosis: Focus on musculoskeletal diseases.","authors":"Zhiwei Liao, Bide Tong, Zixuan Ou, Junyu Wei, Ming Lei, Cao Yang","doi":"10.1111/tra.12905","DOIUrl":"https://doi.org/10.1111/tra.12905","url":null,"abstract":"Iron homeostasis is crucial for maintaining proper cellular function, and its disruption is considered one of the pathogenic mechanisms underlying musculoskeletal diseases. Under conditions of oxidative stress, the accumulation of cellular iron overload and lipid peroxidation can lead to ferroptosis. Extracellular vesicles (EVs), serving as mediators in the cell‐to‐cell communication, play an important role in regulating the outcome of cell ferroptosis. Growing evidence has proven that EV biogenesis and secretion are tightly associated with cellular iron export. Furthermore, different sources of EVs deliver diverse cargoes to bring about phenotypic changes in the recipient cells, either activating or inhibiting ferroptosis. Thus, delivering therapies targeting ferroptosis through EVs may hold significant potential for treating musculoskeletal diseases. This review aims to summarize current knowledge on the role of EVs in iron homeostasis and ferroptosis, as well as their therapeutic applications in musculoskeletal diseases, and thereby provide valuable insights for both research and clinical practice.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 9","pages":"384-396"},"PeriodicalIF":4.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9944277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Crucial roles of Rab22a in endosomal cargo recycling.","authors":"Lingjie Kong, Shenghao Huang, Yuxuan Bao, Yingtong Chen, Chunyan Hua, Sheng Gao","doi":"10.1111/tra.12907","DOIUrl":"https://doi.org/10.1111/tra.12907","url":null,"abstract":"<p><p>Endosomal cargo recycling lies at the heart of subcellular trafficking processes under the management of several Ras-related GTP-binding proteins (Rabs) which are coordinated by their upstream regulators and require their downstream effectors to display their functions. In this regard, several Rabs have been well-reviewed except Rab22a. Rab22a is a crucial regulator of vesicle trafficking, early endosome and recycling endosome formation. Notably, recent studies demonstrated the immunological roles of Rab22a, which are closely associated with cancers, infection and autoimmune disorders. This review provides an overview of the regulators and effectors of Rab22a. Also, we highlight the current knowledge of the role of Rab22a in endosomal cargo recycling, including the biogenesis of recycling tubules with the help of a complex with Rab22a at its core, and how different internalized cargo chooses different recycling routes thanks to the cooperation of Rab22a, its effectors and its regulators. Of note, contradictions and speculation related to endosomal cargo recycling that Rab22a brings impacts on are also discussed. Finally, this review endeavors to briefly introduce the various events impacted by Rab22a, particularly focusing on the commandeered Rab22a-associated endosomal maturation and endosomal cargo recycling, in addition to the extensively investigated oncogenic role of Rab22a.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 9","pages":"397-412"},"PeriodicalIF":4.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9944280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-09-01DOI: 10.1111/tra.12904
Simei Go, Hang Lam Li, Jung-Chin Chang, Arthur J Verhoeven, Ronald P J Oude Elferink
{"title":"Cholangiocytes express an isoform of soluble adenylyl cyclase that is N-linked glycosylated and secreted in extracellular vesicles.","authors":"Simei Go, Hang Lam Li, Jung-Chin Chang, Arthur J Verhoeven, Ronald P J Oude Elferink","doi":"10.1111/tra.12904","DOIUrl":"https://doi.org/10.1111/tra.12904","url":null,"abstract":"<p><p>Soluble adenylyl cyclase (sAC)-derived cAMP regulates various cellular processes; however, the regulatory landscape mediating sAC protein levels remains underexplored. We consistently observed a 85 kD (sAC<sub>85</sub> ) or 75 kD (sAC<sub>75</sub> ) sAC protein band under glucose-sufficient or glucose-deprived states, respectively, in H69 cholangiocytes by immunoblotting. Deglycosylation by PNGase-F demonstrated that both sAC<sub>75</sub> and sAC<sub>85</sub> are N-linked glycosylated proteins with the same polypeptide backbone. Deglycosylation with Endo-H further revealed that sAC<sub>75</sub> and sAC<sub>85</sub> carry distinct sugar chains. We observed release of N-linked glycosylated sAC (sAC<sub>EV</sub> ) in extracellular vesicles under conditions that support intracellular sAC<sub>85</sub> (glucose-sufficient) as opposed to sAC<sub>75</sub> (glucose-deprived) conditions. Consistently, disrupting the vesicular machinery affects the maturation of intracellular sAC and inhibits the release of sAC<sub>EV</sub> into extracellular vesicles. The intracellular turnover of sAC<sub>85</sub> is extremely short (t<sub>1/2</sub> ~30 min) and release of sAC<sub>EV</sub> in the medium was detected within 3 h. Our observations support the maturation and trafficking in cholangiocytes of an N-linked glycosylated sAC isoform that is rapidly released into extracellular vesicles.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 9","pages":"413-430"},"PeriodicalIF":4.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9944282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-08-01DOI: 10.1111/tra.12889
Tatiana Burrinha, César Cunha, Michael J Hall, Mafalda Lopes-da-Silva, Miguel C Seabra, Cláudia Guimas Almeida
{"title":"Deacidification of endolysosomes by neuronal aging drives synapse loss.","authors":"Tatiana Burrinha, César Cunha, Michael J Hall, Mafalda Lopes-da-Silva, Miguel C Seabra, Cláudia Guimas Almeida","doi":"10.1111/tra.12889","DOIUrl":"https://doi.org/10.1111/tra.12889","url":null,"abstract":"<p><p>Previously, we found that age-dependent accumulation of beta-amyloid is not sufficient to cause synaptic decline. Late-endocytic organelles (LEOs) may be driving synaptic decline as lysosomes (Lys) are a target of cellular aging and relevant for synapses. We found that LAMP1-positive LEOs increased in size and number and accumulated near synapses in aged neurons and brains. LEOs' distal accumulation might relate to the increased anterograde movement in aged neurons. Dissecting the LEOs, we found that late-endosomes accumulated while there are fewer terminal Lys in aged neurites, but not in the cell body. The most abundant LEOs were degradative Lys or endolysosomes (ELys), especially in neurites. ELys activity was reduced because of acidification defects, supported by the reduction in v-ATPase subunit V0a1 with aging. Increasing the acidification of aged ELys recovered degradation and reverted synaptic decline, while alkalinization or v-ATPase inhibition, mimicked age-dependent Lys and synapse dysfunction. We identify ELys deacidification as a neuronal mechanism of age-dependent synapse loss. Our findings suggest that future therapeutic strategies to address endolysosomal defects might be able to delay age-related synaptic decline.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 8","pages":"334-354"},"PeriodicalIF":4.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10126393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-08-01DOI: 10.1111/tra.12902
Sally Badawi, Feda E Mohamed, Divya Saro Varghese, Bassam R Ali
{"title":"Genetic disruption of mammalian endoplasmic reticulum-associated protein degradation: Human phenotypes and animal and cellular disease models.","authors":"Sally Badawi, Feda E Mohamed, Divya Saro Varghese, Bassam R Ali","doi":"10.1111/tra.12902","DOIUrl":"https://doi.org/10.1111/tra.12902","url":null,"abstract":"<p><p>Endoplasmic reticulum-associated protein degradation (ERAD) is a stringent quality control mechanism through which misfolded, unassembled and some native proteins are targeted for degradation to maintain appropriate cellular and organelle homeostasis. Several in vitro and in vivo ERAD-related studies have provided mechanistic insights into ERAD pathway activation and its consequent events; however, a majority of these have investigated the effect of ERAD substrates and their consequent diseases affecting the degradation process. In this review, we present all reported human single-gene disorders caused by genetic variation in genes that encode ERAD components rather than their substrates. Additionally, after extensive literature survey, we present various genetically manipulated higher cellular and mammalian animal models that lack specific components involved in various stages of the ERAD pathway.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 8","pages":"312-333"},"PeriodicalIF":4.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9752059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}