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| Open AccessRab30 facilitates lipid homeostasis during fasting
Despite the importance of Rab GTPases in maintaining the integrity of vesicle trafficking, their physiological roles are not well understood. Here, the authors define a role for Rab30 in supporting lipid homeostasis during fasting in the mouse.
- Danielle M. Smith
- , Brian Y. Liu
- & Michael J. Wolfgang
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Matters Arising
| Open AccessReply to: Does the KDEL receptor cycle between the Golgi and the ER?
- Jurgen Denecke
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Article
| Open AccessTBC1D23 mediates Golgi-specific LKB1 signaling
The LKB1 signaling is differentially regulated and has distinct functions at different subcellular compartments. Tu et al reports that TBC1D23 specifically regulates Golgi-LKB1 signaling and link this pathway to neurodevelopment disorders.
- Yingfeng Tu
- , Qin Yang
- & Da Jia
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Article
| Open AccessProteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly
Here, the authors uncover that, among 92 identified host factors associated with SARS-CoV-2 virions, G3BP1 and G3BP2 are present at the assembly site, incorporated within virions, and unexpectedly promote the production of SARS-CoV-2 virions.
- Emilie Murigneux
- , Laurent Softic
- & Sarah Gallois-Montbrun
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Article
| Open AccessSingle-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol
Stimulator of interferon genes (STING) is known to translocate from ER to Golgi while orchestrating type I interferon responses to DNA. Here, the authors show single-molecule resolution images of STING clustering at the trans-Golgi network, where it acts as a scaffold to trigger downstream signaling.
- Haruka Kemmoku
- , Kanoko Takahashi
- & Tomohiko Taguchi
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Article
| Open AccessA single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs
Dey et al. use structure-function methods to show that partial mimicry of the coatomer-binding motif in the SARS-CoV-2 spike is crucial for its release post coatomer-dependent delivery, thus ensuring optimal spike fusogenicity and VLP incorporation.
- Debajit Dey
- , Enya Qing
- & S. Saif Hasan
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Article
| Open AccessRegulation of cellular cholesterol distribution via non-vesicular lipid transport at ER-Golgi contact sites
The molecular mechanisms responsible for cellular cholesterol distribution remain unclear. Here, the authors identify a key role of lipid transfer proteins ORP9, OSBP, and GRAMD1s in maintaining cholesterol levels in the Golgi and plasma membrane.
- Tomoki Naito
- , Haoning Yang
- & Yasunori Saheki
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Article
| Open AccessDeep and fast label-free Dynamic Organellar Mapping
Regulated subcellular localization changes control protein function. Here, the authors provide a seamless spatial proteomics pipeline for mapping whole-cell protein localization dynamics, which includes a scalable workflow and a software suite for automated data analysis and visualization.
- Julia P. Schessner
- , Vincent Albrecht
- & Georg H. H. Borner
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Article
| Open AccessLoss of the batten disease protein CLN3 leads to mis-trafficking of M6PR and defective autophagic-lysosomal reformation
CLN3 mutations cause Batten disease, a devastating neurodegenerative lysosomal storage disease. Here, the authors discovered that CLN3 plays a crucial role in both trafficking of lysosomal proteins and autophagic lysosomal reformation.
- Alessia Calcagni’
- , Leopoldo Staiano
- & Andrea Ballabio
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Article
| Open AccessZinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface
Zinc is vital to protein quality control in the early secretory pathway. Here, authors demonstrate distinct roles of the Golgi-resident zinc transporters for the maintenance of zinc homeostasis and the regulation of a zinc-dependent chaperone, ERp44.
- Yuta Amagai
- , Momo Yamada
- & Kenji Inaba
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Article
| Open AccessThe K/HDEL receptor does not recycle but instead acts as a Golgi-gatekeeper
In contrast to the current model based on fast recycling of the K/HDEL receptor (ERD2) between the ER and the Golgi apparatus, here authors show evidence that ERD2 is specifically retained in the Golgi apparatus and evades joining its ligands en route to the ER.
- Jonas C. Alvim
- , Robert M. Bolt
- & Jurgen Denecke
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Article
| Open AccessMicrotubule nucleation and γTuRC centrosome localization in interphase cells require ch-TOG
The molecular mechanisms underpinning the organization of microtubule arrays remain unclear. Here the authors show that in human cells, the microtubule polymerase ch-TOG promotes nucleation of microtubules at the interphase centrosome and the Golgi through a mechanism that involves transient interaction with the microtubule nucleator γTuRC.
- Aamir Ali
- , Chithran Vineethakumari
- & Jens Lüders
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Article
| Open AccessInterruption of post-Golgi STING trafficking activates tonic interferon signaling
Microbial DNA is recognized by the cGAS-STING pathway, which leads to a type I interferon response. Here authors show that a basal flux of interferon activation could also be triggered by interference with STING trafficking from the Golgi apparatus to the lysosomes.
- Xintao Tu
- , Ting-Ting Chu
- & Nan Yan
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Article
| Open AccessDominant ARF3 variants disrupt Golgi integrity and cause a neurodevelopmental disorder recapitulated in zebrafish
Disruptions to the ER-Golgi network can lead to neurodevelopmental disorders, though our understanding of these Golgipathies remains incomplete. Here Lauri, Tartaglia and colleagues show that ARF3 mutations cause a rare pediatric neurological disorder and perform detailed molecular characterization in fish.
- Giulia Fasano
- , Valentina Muto
- & Marco Tartaglia
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Article
| Open AccessSmall extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1
The pathological mechanisms that lead to Ossification of the posterior longitudinal ligament (OPLL) are unclear. Here, the authors show that OPLL ligament cells produce small extracellular vesicles that induce ossification via miR-320e/TAK1 signaling in mice and human posterior longitudinal ligament cells.
- Chen Xu
- , Zicheng Zhang
- & Wen Yuan
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Article
| Open AccessCul3-KLHL20 E3 ubiquitin ligase plays a key role in the arms race between HIV-1 Nef and host SERINC5 restriction
SERINC5 is a host-restriction factor preventing HIV progeny entry, which is counteracted by interactions with HIV Nef. Here, Li et al. show that E3 ubiquitin ligase Cullin 3 polyubiquitinates SERINC5 at Lys 130 via K48- and K33-linked ubiquitin chains and provide evidence that this modification is not only required for its membrane localization and anti-viral activity but also relevant for Nef counteractive activity.
- Sunan Li
- , Rongrong Li
- & Yong-Hui Zheng
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Article
| Open AccessUBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony
Although ubiquitin ligases are known to control clock protein degradation, their other roles in clock neurons are unclear. Here the authors report that UBR4 promotes export of neuropeptides from the Golgi for axonal trafficking, which is important for circadian clock synchrony in mice and flies.
- Sara Hegazi
- , Arthur H. Cheng
- & Hai-Ying Mary Cheng
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Article
| Open AccessWFS1 functions in ER export of vesicular cargo proteins in pancreatic β-cells
The role of cargo receptors in proinsulin export from the ER is unclear. Here, the authors identify the WFS1 protein, which is mutated in Wolfram syndrome and associated with diabetes, as an ER to Golgi cargo receptor required for normal insulin processing and secretion.
- Linlin Wang
- , Hongyang Liu
- & Zonghong Li
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Article
| Open AccessCongenital disorder of glycosylation caused by starting site-specific variant in syntaxin-5
Mutations in genes critical for proper intra-Golgi transport can cause human syndromes due to defects in glycosylation of proteins. Here, the authors identify a human variant of Syntaxin-5 that causes fatal multisystem disease and mislocalization of glycosyltransferases due to altered Golgi transport.
- Peter T. A. Linders
- , Eveline C. F. Gerretsen
- & Geert van den Bogaart
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Article
| Open AccessSequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation
The Spike protein of SARS-CoV-2 has a C-terminal cytoplasmic tail. Here the authors show that this tail binds trafficking machinery via sequences that appear optimised to ensure that Spike accumulates at the site of viral budding in the Golgi but that some can also traffic to the cell surface to induce syncytia formation.
- Jérôme Cattin-Ortolá
- , Lawrence G. Welch
- & Sean Munro
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Article
| Open AccessSphingolipids mediate polar sorting of PIN2 through phosphoinositide consumption at the trans-Golgi network
Lipid composition impacts the function of cellular membranes. Here the authors show that a reduction in sphingolipid acyl-chain length promotes phosphoinositide consumption by phospholipase C at the Arabidopsis trans-Golgi network which in turn regulates sorting of the auxin efflux carrier PIN2.
- Yoko Ito
- , Nicolas Esnay
- & Yohann Boutté
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Article
| Open AccessCargo sorting zones in the trans-Golgi network visualized by super-resolution confocal live imaging microscopy in plants
The trans-Golgi network (TGN) serves as a platform to sort and transport proteins to their final destinations. Here the authors show that the TGN of Arabidopsis consists of spatially and temporally distinct subregions and propose that these zones may sort cargo to different destinations.
- Yutaro Shimizu
- , Junpei Takagi
- & Akihiko Nakano
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Article
| Open AccessHomeostatic regulation of STING by retrograde membrane traffic to the ER
COPA regulates Golgi to ER transport, and mutations lead to autoinflammation and disease through poorly understood mechanisms. Here, the authors show that disease-causing COPA variants prevent STING transport from the Golgi to the ER, leading to cGAS-independent activation of the STING pathway.
- Kojiro Mukai
- , Emari Ogawa
- & Tomohiko Taguchi
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Article
| Open AccessMutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
p53 mutants can promote tumorigenesis by affecting fundamental cellular pathways and functions. In this study, the authors demonstrate a novel mutant-p53/HIF1α/miR-30d axis that impacts Golgi structure, trafficking, and secretion of proteins essential for tumor growth and metastasis.
- Valeria Capaci
- , Lorenzo Bascetta
- & Giannino Del Sal
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Article
| Open AccessGolgi organization is regulated by proteasomal degradation
Correct Golgi assembly is important to cellular homeostasis but regulation of its structure under stress remains unclear. Here, the authors identify stress-induced degradation of GM130 by Golgi-localized 26S proteasomes, leading to Golgi dispersal.
- Avital Eisenberg-Lerner
- , Ron Benyair
- & Yifat Merbl
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Article
| Open AccessRan pathway-independent regulation of mitotic Golgi disassembly by Importin-α
Golgi disassembly is required for mitosis and occurs by vesicle fusion suppression, although the mechanism is unclear. Here, Chang et al. show, with quantitative analyses and crystallography, that Importin-α regulates this process by blocking GM130-p115 interactions in a Ran pathway-independent way.
- Chih-Chia Chang
- , Ching-Jou Chen
- & Kuo-Chiang Hsia
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Article
| Open AccessALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis
Intracellular vesicle transport can be regulated by Brefeldin‐A ADP‐Ribosylated Substrate (BARS) during vesicle fission. Here, the authors show that NADH generated by aldehyde dehydrogenase 7A1 (ALDH7A1) inhibits intracellular transport by targeting BARS and inhibiting COPI vesicle fission during situations of energy deprivation
- Jia-Shu Yang
- , Jia-Wei Hsu
- & Victor W. Hsu
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Article
| Open AccessThe late stage of COPI vesicle fission requires shorter forms of phosphatidic acid and diacylglycerol
Phosphatidic acid and diacylglycerol are required for COPI vesicle fission. Here, the authors find that shorter forms of these lipids promote the late stage of COPI vesicle fission, further suggesting how lipid geometry contributes to membrane deformation in driving fission.
- Seung-Yeol Park
- , Jia-Shu Yang
- & Victor W. Hsu
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Article
| Open AccessLysosomal degradation of newly formed insulin granules contributes to β cell failure in diabetes
Impaired beta-cell insulin secretion is a key pathological feature of type 2 diabetes. Here, the authors describe metabolic stress induced lysosomal degradation of newly formed insulin granules, independent of macroautophagy, as a potential mechanism for beta-cell dysfunction.
- Adrien Pasquier
- , Kevin Vivot
- & Romeo Ricci
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Article
| Open AccessGORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation
COPI is recruited to the membrane by binding to Arf GTPases. Here the authors find that GORAB, a trans-Golgi protein, promotes COPI recruitment by forming membrane domains that also contain the COPI-interacting protein Scyl1, which is required for efficient glycosylation of cargo proteins.
- Tomasz M. Witkos
- , Wing Lee Chan
- & Martin Lowe
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Article
| Open AccessAmino acids stimulate the endosome-to-Golgi trafficking through Ragulator and small GTPase Arl5
Amino acid levels are known to regulate anabolic and catabolic pathways. Here, the authors report that amino acids also affect membrane trafficking by stimulating endosome-to-Golgi retrograde trafficking and regulating cell surface localization of certain Golgi proteins through Ragulator and Arl5.
- Meng Shi
- , Bing Chen
- & Lei Lu
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Article
| Open AccessNuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role
Cytoplasmic PTEN is a tumor suppressor that antagonises PI3K signalling. Here, the authors show that nuclear PTEN can interact with the spliceosomal proteins and drive pre-mRNA splicing in a phosphatase-independent manner, in particular, PTEN depletion promotes Golgi extension and secretion through GOLGA2 exon skipping.
- Shao-Ming Shen
- , Yan Ji
- & Guo-Qiang Chen
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Article
| Open AccessNanobody-triggered lockdown of VSRs reveals ligand reloading in the Golgi
Vacuolar sorting receptors (VSRs) are suggested to efficiently transport hydrolases by continuous cycling. Here, the authors use a nanobody-epitope interaction-based labeling approach to trace VSR recycling from the TGN/EE to the cis-Golgi and reveal ligand reloading of recycled VSRs.
- Simone Früholz
- , Florian Fäßler
- & Peter Pimpl
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Article
| Open AccessCoupling fission and exit of RAB6 vesicles at Golgi hotspots through kinesin-myosin interactions
Actin and microtubules play important roles in Golgi structure and function but how they are connected is poorly understood. Here the authors show that KIF20A is involved in the fission process and, in association with Myosin II, serves to anchor RAB6 on Golgi/TGN membranes near microtubules nucleating sites.
- Stéphanie Miserey-Lenkei
- , Hugo Bousquet
- & Bruno Goud
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Article
| Open AccessThe catalytic subunit of DNA polymerase δ inhibits γTuRC activity and regulates Golgi-derived microtubules
Microtubule organization requires γ-tubulin ring complexes (γTuRCs), but the mechanisms that control γTuRC-mediated microtubule nucleation are unclear. Here the authors show that the DNA polymerase δ catalytic subunit controls noncentrosomal γTuRC activity and regulates the organization of Golgi-derived microtubules.
- Yuehong Shen
- , Pengfei Liu
- & Robert Z. Qi
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Article
| Open AccessLand-locked mammalian Golgi reveals cargo transport between stable cisternae
The different composition of Golgi cisternae gave rise to two different models for intra-Golgi traffic: one where stable cisternae communicate via vesicles and another one where cisternae biochemically mature to ensure anterograde transport. Here, the authors provide evidence in support of the stable compartments model.
- Myun Hwa Dunlop
- , Andreas M. Ernst
- & James E. Rothman
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Article
| Open AccessRouting of the RAB6 secretory pathway towards the lysosome related organelle of melanocytes
The anterograde movement of Golgi-derived vesicles requires the small GTPase RAB6, while its effector ELKS targets these vesicles to particular areas of the plasma membrane. Here the authors show that RAB6 and ELKS function in the biogenesis of melanosome, demonstrating that the secretory pathway can be directed towards intracellular organelles of endosomal origin.
- Anand Patwardhan
- , Sabine Bardin
- & Cédric Delevoye
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Article
| Open AccessA mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi
VPS15 is known as a VPS34-associated protein that functions in intracellular trafficking and autophagy. Here the authors identify a role for VPS15 in ciliopathy and ciliary phenotypes, and show that it interacts with GM130 and functions in IFT20-dependent cis-Golgi to cilium trafficking.
- Corinne Stoetzel
- , Séverine Bär
- & Hélène Dollfus
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Article
| Open AccessEnrichment of hydroxylated C24- and C26-acyl-chain sphingolipids mediates PIN2 apical sorting at trans-Golgi network subdomains
Sphingolipids in the trans-Golgi network have been implicated in polar trafficking. Here Wattelet-Boyer et al. show that hydroxylated C24- and C26-acyl-chain sphingolipids are enriched in trans-Golgi network subdomains that are critical for polar sorting of the PIN2 auxin carrier in plant cells.
- Valérie Wattelet-Boyer
- , Lysiane Brocard
- & Yohann Boutté
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Article
| Open AccessActivation of STING requires palmitoylation at the Golgi
STING is essential for the type I interferon immune response to foreign DNA. Here, the authors show that palmitoylation of STING at the Golgi is required for activating downstream signalling, and increased Golgi localization of certain STING variants may cause autoimmune disease in some cases.
- Kojiro Mukai
- , Hiroyasu Konno
- & Tomohiko Taguchi
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Article
| Open AccessGolgi-localized STELLO proteins regulate the assembly and trafficking of cellulose synthase complexes in Arabidopsis
Cellulose is produced in plants by cellulose synthase complexes (CSCs) that are assembled in the endomembrane system and then trafficked to the plasma membrane. Here Zhang et al. show that the Golgi-localized STELLO1 and 2 proteins are required for the proper assembly and distribution of CSCs in plant cells.
- Yi Zhang
- , Nino Nikolovski
- & Paul Dupree
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Article
| Open AccessAurora-A recruitment and centrosomal maturation are regulated by a Golgi-activated pool of Src during G2
The Golgi mitotic checkpoint couples Golgi inheritance with cell cycle transition, and regulates centrosomal recruitment of the mitotic kinase Aurora-A. Here the authors show that upon Golgi ribbon fragmentation in G2, Src phosphorylates Aurora-A at the Golgi, driving its localization to the centrosomes.
- Maria Luisa Barretta
- , Daniela Spano
- & Antonino Colanzi
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Article
| Open AccessFAM21 directs SNX27–retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus
Endosomes maintain cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Here the authors show that the SNX27-retromer-WASH complex acts as a hub to direct cargoes to the plasma membrane by blocking their transport to lysosomes and Golgi apparatus.
- Seongju Lee
- , Jaerak Chang
- & Craig Blackstone
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Article
| Open AccessPAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the Golgi apparatus
Under conditions of sterol depletion, the Scap/SREBP complex is transported from the endoplasmic reticulum to the Golgi apparatus. Here Xu and Wang et al.show that the Golgi protein PAQR3 interacts with Scap and SREBP in a cholesterol regulated manner to help regulate sterol homeostasis.
- Daqian Xu
- , Zheng Wang
- & Yan Chen
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A phosphatidylinositol-4-phosphate powered exchange mechanism to create a lipid gradient between membranes
The lipid transfer protein Osh4p is able to exchange sterol, made at the endoplasmic reticulum, for Golgi-synthesized PI(4)P. Here the authors provide direct evidence that Osh4p can transport sterol against its concentration gradient between membranes, powered by dissipation of a PI(4)P gradient.
- Joachim Moser von Filseck
- , Stefano Vanni
- & Guillaume Drin
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Article
| Open AccessCiliary membrane proteins traffic through the Golgi via a Rabep1/GGA1/Arl3-dependent mechanism
Polycystins (PC) 1 and 2 are large transmembrane proteins that play a vital role in the function of primary cilia. Here, Kim et al. identify the requirements for polycystin trafficking to the cilium, involving a PC1–PC2 interaction, PC1 proteolytic cleavage and a specific trafficking module at the trans-Golgi network.
- Hyunho Kim
- , Hangxue Xu
- & Feng Qian
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Article |
MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane
Microtubules that nucleate from the surface of the Golgi network are important for polarized trafficking and cell migration. Sato et al.find that these microtubules are crosslinked and stabilized by the microtubule-binding protein MTCL1, and show that this activity is required for Golgi structure and function.
- Yoshinori Sato
- , Kenji Hayashi
- & Atsushi Suzuki
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Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development
Polarized membrane addition during axon development requires post-Golgi Rab10 carriers, whose biogenesis mechanisms remain unknown. This work shows that specific interaction between Rab10 and MYO5B controls formation of the Rab10 carriers, and this process is essential for neuronal polarization.
- Yang Liu
- , Xiao-Hui Xu
- & Zhen-Ge Luo
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Regulation of protein glycosylation and sorting by the Golgi matrix proteins GRASP55/65
GRASP proteins are thought to play a role in maintaining the stacked structure of the Golgi complex. Xiang et al. discover that depletion of GRASPs accelerates Golgi traffic, but reduces the complexity of Golgi protein glycosylation.
- Yi Xiang
- , Xiaoyan Zhang
- & Yanzhuang Wang