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Article
| Open Access
Zinc 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 Access
A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience
Environmental temperature changes can alter cell membrane lipid composition but the mechanisms underlying this conserved mechanism are unclear. Here, the authors identify the megaprotein LPD-3 in C. elegans as critical for normal phospholipid distribution and cold resilience.
- Changnan Wang
- , Bingying Wang
- & Dengke K. Ma
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Article
| Open Access
The lysosomal transporter TAPL has a dual role as peptide translocator and phosphatidylserine floppase
In this work, the authors report an ATP-dependent phosphatidylserine floppase activity for the lysosomal ATP-binding cassette transporter TAPL. In addition, they report the cryo-EM structures of mouse TAPL complexed with (i) phospholipid, (ii) cholesteryl hemisuccinate (CHS) and 9-mer peptide, and (iii) ADP·BeF3. Together, their results suggest that TAPL uses different mechanisms to function as a peptide translocase and a phosphatidylserine floppase.
- Jun Gyou Park
- , Songwon Kim
- & Mi Sun Jin
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Article
| Open Access
Structural basis for mitoguardin-2 mediated lipid transport at ER-mitochondrial membrane contact sites
The ER-mitochondria contact sites are crucial for exchanging phospholipids. Here, Kim et al. present crystal structures of mitoguardin-2 (MIGA2) which reveal that MIGA2 directly binds phospholipids and transfers them between the ER and mitochondria.
- Hyunwoo Kim
- , Seowhang Lee
- & Changwook Lee
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Article
| Open Access
WFS1 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 Access
TRAPPC4 regulates the intracellular trafficking of PD-L1 and antitumor immunity
Transport protein particle (TRAPP) is a multimeric protein complex regulating membrane trafficking pathways. Here the authors show that TRAPPC4, a core subunit of TRAPP complex, is required for RAB11-mediated recycling of PD-L1, affecting T-cell-mediated anti-tumor immune responses.
- Yimeng Ren
- , Yun Qian
- & Jing-Yuan Fang
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Article
| Open Access
Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis
Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Here, the authors show that Cdk5 and GSK3β are negative regulators of fast Endophilin-mediated endocytosis (FEME).
- Antonio P. A. Ferreira
- , Alessandra Casamento
- & Emmanuel Boucrot
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Article
| Open Access
Structure of the complete, membrane-assembled COPII coat reveals a complex interaction network
Cytosolic coat proteins capture secretory cargo and sculpt membrane carriers for intracellular transport, such as COPII which mediates Endoplasmic Reticulum to Golgi trafficking of thousands of cargoes. Here authors visualise the complete, membrane-assembled COPII coat by cryo-electron tomography and subtomogram averaging, revealing the full network of interactions within and between coat layers.
- Joshua Hutchings
- , Viktoriya G. Stancheva
- & Giulia Zanetti
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Article
| Open Access
Dopey1-Mon2 complex binds to dual-lipids and recruits kinesin-1 for membrane trafficking
Proteins are transported among eukaryotic organelles along the cytoskeleton in membrane carriers. Here authors find that the Dopey1-Mon2 complex functions as a dual-lipid-regulated cargo-adaptor to recruit kinesin-1 to secretory and endocytic organelles or membrane carriers.
- Divyanshu Mahajan
- , Hieng Chiong Tie
- & Lei Lu
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Article
| Open Access
Improvement and extension of anti-EGFR targeting in breast cancer therapy by integration with the Avidin-Nucleic-Acid-Nano-Assemblies
The nature of the linker is known to affect the efficacy of antibody–drug conjugate (ADC). Here the authors show cetuximab-guided Avidin-Nucleic-Acid-Nanoassemblies to be superior to cetuximab-doxorubicin conjugate, and show its efficacy in KRAS mutant breast cancer, allowing for therapeutic expansion of anti-EGFR therapy.
- Francesco Roncato
- , Fatlum Rruga
- & Margherita Morpurgo
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Article
| Open Access
Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions
The CORVET complex is a multi-subunit complex that regulates fusion between early endosomes. Here the authors show that the CORVET subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes and are required for recycling integrins to the plasma membrane.
- Caspar T. H. Jonker
- , Romain Galmes
- & Judith Klumperman
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Article
| Open Access
Steric exclusion and protein conformation determine the localization of plasma membrane transporters
The yeast plasma membrane consists of membrane microdomains with distinct protein composition. Here the authors use high-resolution single molecule imaging to observe diffusion of specific transmembrane proteins in and out of these microdomains, and propose features that dictate their inclusion/exclusion from these structures.
- Frans Bianchi
- , Łukasz Syga
- & Bert Poolman
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Article
| Open Access
Coupling 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 Access
Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration
The endocytic adaptor protein complex AP-2 is mostly known for its role in endocytosis and in synaptic vesicle reformation. Here the authors show that AP-2 also mediates retrograde transport of TrkB-containing autophagosomes in neurons; this process promotes neuronal complexity and prevents the degeneration of cortical and thalamic neurons.
- Natalia L. Kononenko
- , Gala A. Claßen
- & Volker Haucke
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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 Access
Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential
The half-life of IgG is regulated by binding to the neonatal Fc receptor and, in the case of IgG3, is reduced compared to other IgG proteins. In this study, a mutation in IgG3 is shown to reduce binding to the neonatal Fc receptor, which can be competitively blocked by IgG1.
- Nigel M. Stapleton
- , Jan Terje Andersen
- & Gestur Vidarsson
LDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments