Protein transport

  • Article
    | Open Access

    NEK1 mutations promote lethality early in life and ALS late in life via unknown mechanisms. Here, the authors show that NEK1 mutation disrupts retromer-mediated trafficking and promotes RIPK1 activation, connecting retromer trafficking and metabolism to neuroinflammation by dietary intervention.

    • Huibing Wang
    • , Weiwei Qi
    •  & Junying Yuan
  • Article
    | Open Access

    The permeability barrier of nuclear pore complexes blocks passage of inert macromolecules but allows rapid, receptor-mediated, and RanGTPase-driven transport of cargoes up to ribosome size. The authors now show that such a barrier can be faithfully recapitulated by an ultimately simplified FG phase assembled solely from a tandemly repeated 12mer GLFG peptide.

    • Sheung Chun Ng
    • , Thomas Güttler
    •  & Dirk Görlich
  • Article
    | Open Access

    Type-III secretion systems (T3SSs) are capable of translocating proteins with high speed while maintaining the membrane barrier for small molecules. Here, a structure-function analysis of the T3SS pore complex elucidates the precise mechanisms enabling the gating and the conformational changes required for protein substrate secretion.

    • Svenja Hüsing
    • , Manuel Halte
    •  & Thibaud T. Renault
  • Article
    | Open Access

    Bacteria use the type 2 secretion system to secrete enzymes and toxins across the outer membrane to the environment. Here the authors analyse the T2SS pathway in three protist lineages and suggest that the early mitochondrion may have been capable of secreting proteins into the cytosol.

    • Lenka Horváthová
    • , Vojtěch Žárský
    •  & Pavel Doležal
  • Article
    | Open Access

    The mechanisms by which platelets release sphingosine-1-phosphate (S1P) is not well characterized. Here the authors show that Mfsd2b is required for S1P release from both resting and activated platelets and that deletion of Mfsd2b impairs thrombotic functions of platelets.

    • Madhuvanthi Chandrakanthan
    • , Toan Quoc Nguyen
    •  & Long N. Nguyen
  • Article
    | Open Access

    Most mitochondrial proteins are imported from the cytosol and must fold in the mitochondria. Here, the authors show that the mitochondrial protease LONP1 plays a critical role in the mtHSP70 chaperone system independently of its protease activity.

    • Chun-Shik Shin
    • , Shuxia Meng
    •  & David C. Chan
  • Article
    | Open Access

    Biochemistry combined with biophysical measurements and mathematical modeling offer insight into the mechanism by which the cotranslational chaperone, nascent polypeptide-associated complex (NAC), modulates substrate selection by signal recognition particle (SRP) and reduces aberrant, nonspecific targeting of ribosomes to the ER.

    • Hao-Hsuan Hsieh
    • , Jae Ho Lee
    •  & Shu-ou Shan
  • Article
    | Open Access

    The transcriptional regulator YAP shuttles rapidly between the cytoplasm and nucleus, but whether and how dynamics such as amplitude and frequency affect target gene transcription is unclear. Here, using live imaging of endogenous YAP and target-gene transcription, the authors show that YAP-dependent signalling is encoded through rapid and concerted changes in the nucleo-cytoplasmic distribution of YAP.

    • J. Matthew Franklin
    • , Rajarshi P. Ghosh
    •  & Jan T. Liphardt
  • Article
    | Open Access

    The ATPase SecA drives Sec-dependent protein translocation across the bacterial plasma membrane. Here, the authors combine kinetic translocation measurements with single-molecule force spectroscopy and demonstrate that the SecA motor generates mechanical force to unfold and translocate preproteins.

    • Riti Gupta
    • , Dmitri Toptygin
    •  & Christian M. Kaiser
  • Article
    | Open Access

    Import of proteins into specific cellular compartments is critical for organelle function and several proteins are known to be imported into multiple compartments. Here, the authors report that the protein Ptc5 is first sorted to and processed in the mitochondria before being targeted to peroxisomes, which may influence mitochondria-peroxisome interorganellar contact.

    • Thorsten Stehlik
    • , Marco Kremp
    •  & Johannes Freitag
  • Article
    | Open Access

    Most cells possess sensory cilia, which need to be gated properly. Here the authors show that the C. elegans proteins TALP-3 and ANKR-26 coordinate cilia gating in the context of transition fibers and that this mechanism is conserved in mammalian cells and likely implicated in certain ciliopathies.

    • Hao Yan
    • , Chuan Chen
    •  & Qing Wei
  • Article
    | Open Access

    The contribution of central and peripheral channels of nuclear pores to transport of transmembrane proteins is unclear. Here the authors show that most inner nuclear membrane proteins use only peripheral channels, but some extend nuclear localization signals into the central channel for directed nuclear transport.

    • Krishna C. Mudumbi
    • , Rafal Czapiewski
    •  & Weidong Yang
  • Article
    | Open Access

    Proteins are translocated across membranes through the Sec61/SecY channel. Here, the authors present the structure of a translocating peptide chain trapped inside the SecA-SecY complex which suggests how peptides are actively moved through the channel.

    • Chengying Ma
    • , Xiaofei Wu
    •  & Long Li
  • Article
    | Open Access

    Synaptic plasticity ensures functionality during perturbations and enables memory formation. Here, the authors describe homeostatic functional and nano-modular active zone modifications for immediate and long-lasting enhancement of neurotransmitter release, and identify Unc13 as a presynaptic molecular target for homeostatic potentiation and learning.

    • Mathias A. Böhme
    • , Anthony W. McCarthy
    •  & Alexander M. Walter
  • Article
    | Open Access

    Cubilin and the transmembrane protein amnionless (AMN) form the endocytic receptor cubam that is essential for intestinal vitamin B12 uptake. Here the authors present the 2.3 Å crystal structure of AMN in complex with the amino-terminal region of cubilin and discuss cubam architecture and disease causing mutations.

    • Casper Larsen
    • , Anders Etzerodt
    •  & Christian Brix Folsted Andersen
  • Article
    | Open Access

    TssA is an important component of the bacterial type VI secretion system (T6SS). Here, Dix et al. integrate structural, phylogenetic and functional analysis of the TssA subunits, providing new insights into their role in T6SS assembly and function.

    • Samuel R. Dix
    • , Hayley J. Owen
    •  & Mark S. Thomas
  • Article
    | Open Access

    While Sec61 enables ER import of all polypeptides with N-terminal signal peptides, only selected clients are accepted for TRAP-assisted ER import. Here, the authors use a proteomics approach to characterize TRAP-dependent clients, identifying signal peptide features that govern recognition by TRAP.

    • Duy Nguyen
    • , Regine Stutz
    •  & Richard Zimmermann
  • Article
    | Open Access

    Microvilli can participate in adhesion or migration of T cells, but whether they are involved in function regulation is unclear. Here the authors show that T cell microvilli form budding vesicles containing T cell signalling components for deposition onto antigen presenting cells (APC) and modulation of APC functions.

    • Hye-Ran Kim
    • , YeVin Mun
    •  & Chang-Duk Jun
  • Article
    | Open Access

    It is not clear whether and how incoming HIV-1 Tat accumulates in uninfected cells. Here, Chopard et al. show that, in uninfected cells, incoming Tat is palmitoylated on Cys31 by DHHC-20, which increases its affinity for PI(4,5)P2 and results in its accumulation at the plasma membrane.

    • Christophe Chopard
    • , Phuoc Bao Viet Tong
    •  & Bruno Beaumelle
  • Article
    | Open Access

    The Bam complex promotes the insertion of β-barrel proteins (such as UpaG, a trimeric autotransporter adhesin) into the bacterial outer membrane. Here, Sikdar et al. show that UpaG β-barrel segments fold into a trimeric structure in the periplasm before they interact with the Bam complex.

    • Rakesh Sikdar
    • , Janine H. Peterson
    •  & Harris D. Bernstein
  • Article
    | Open Access

    The contribution of metabolic pathways to protein secretion is largely unknown. Here, the authors find conserved metabolic patterns in yeast by examining genome-wide transcriptional responses in high protein secretion mutants and reveal critical factors that can be tuned for efficient protein secretion.

    • Mingtao Huang
    • , Jichen Bao
    •  & Jens Nielsen
  • Article
    | Open Access

    PEX19 is a chaperone and import receptor for peroxisomal membrane proteins (PMPs). Here the authors present the structure of the farnesylated C-terminal domain of PEX19, and its interaction with PMPs reveals how the farnesyl moiety allosterically reshapes the PMP binding surface and modulates PEX19 function.

    • Leonidas Emmanouilidis
    • , Ulrike Schütz
    •  & Michael Sattler
  • Article
    | Open Access

    The translocon-associated protein complex (TRAP) is a crucial component of the endoplasmic reticulum protein translocon. Here the authors study native translocon structures from human disease patients and algae cells to determine the molecular organization of the TRAP complex.

    • Stefan Pfeffer
    • , Johanna Dudek
    •  & Friedrich Förster
  • Article
    | Open Access

    Inhibition of PI3K/mTOR, which mimics nutrient starvation, causes death of detached but not matrix-attached cancer cells. Here the authors show that nutrient restriction of epithelial cells causes uptake of the matrix protein laminin, which results in increased intracellular amino acids and enhanced mTORC1 signalling.

    • Taru Muranen
    • , Marcin P. Iwanicki
    •  & Nada Y. Kalaany
  • Article
    | Open Access

    The mitochondrial protein import machinery is crucial for eukaryotes but little is known about its evolutionary origin. Here, the authors characterize the translocase of the inner membrane (TIM) in trypanosomes, showing that it contains two rhomboid-like proteins essential for protein import.

    • Anke Harsman
    • , Silke Oeljeklaus
    •  & André Schneider
  • Article
    | Open Access

    The water channel AQP2 mediates the concentration of urine in the kidney. Here Ando et al. show that Wnt5 promotes collecting duct permeability by regulating AQP2 expression and localization through activation of the calmodulin/calcineurin signalling pathway.

    • Fumiaki Ando
    • , Eisei Sohara
    •  & Shinichi Uchida
  • Article
    | Open Access

    The transport of secretory proteins from the endoplasmic reticulum to the Golgi depends on COPII-coated vesicles. Here, the authors show that activation-induced alternative splicing of Sec16 controls adaptation of COPII transport to increased secretory cargo upon T cell activation.

    • Ilka Wilhelmi
    • , Regina Kanski
    •  & Florian Heyd
  • Article
    | Open Access

    Reactive oxygen species (ROS) damage cell components, necessitating their clearance through autophagy. Here, the authors show that ROS can induce autophagy by triggering TRPML1 to release Ca2+from the lysosomal lumen, in turn activating the autophagy and lysosomal biogenesis regulator TFEB.

    • Xiaoli Zhang
    • , Xiping Cheng
    •  & Haoxing Xu
  • Article
    | Open Access

    Single cells can display large heterogeneity in gene induction. Here, Aymoz et al. present an expression reporter based on protein translocation that can accurately measure both the levels and dynamics of protein synthesis in live single cells with a temporal resolution of less than one minute.

    • Delphine Aymoz
    • , Victoria Wosika
    •  & Serge Pelet
  • Article
    | Open Access

    The temperature-sensitive TRPM8 channel is essential for cold sensing and has been linked to pathological cold hypersensitivity. Here, the authors find TRPM8 insertion in the cell membrane is mediated by VAMP7 following atypical LAMP1-containing vesicle transport, and that loss of VAMP7 leads to reduced cold avoidance in vivo.

    • Debapriya Ghosh
    • , Silvia Pinto
    •  & Thomas Voets
  • Article
    | Open Access

    Export of Plasmodium falciparum proteins into infected erythrocytes relies upon the PEXEL motif in target proteins. Here Boddey et al.challenge the hypothesis that the PEXEL motif mediates export by binding PI(3)P and instead suggest it acts via cleavage by plasmepsin V.

    • Justin A. Boddey
    • , Matthew T. O’Neill
    •  & Alan F. Cowman
  • Article
    | Open Access

    While ERK signalling can produce switch-like cell behaviour, phosphorylation of ERK increases linearly with extracellular signals. Here, the authors solve this seeming contradiction by showing that nuclear translocation of ERK behaves in a switch-like manner and is controlled by ERK activity.

    • Yuki Shindo
    • , Kazunari Iwamoto
    •  & Koichi Takahashi
  • Article
    | Open Access

    Chemotherapeutic agents elicit ER and oxidative stress as part of their mode of action. Here the authors show that chemotherapy and ER stress trigger MGST2-based biosynthesis of LTC4, whose inhibition abolishes chemotherapy- and ER stress-triggered oxidative stress and DNA damage, resulting in the attenuation of cell death.

    • Efrat Dvash
    • , Michal Har-Tal
    •  & Menachem Rubinstein
  • Article
    | Open Access

    The protein-conducting channel Sec61 is responsible for protein transport and membrane insertion at the endoplasmic reticulum. Here, the authors determine the structure of ribosome-bound Sec61 in a native context, in which it adopts a laterally open conformation, irrespective of its functional state.

    • Stefan Pfeffer
    • , Laura Burbaum
    •  & Friedrich Förster
  • Article
    | Open Access

    Endocytosis typically directs proteins on a recycling route back to the plasma membrane, transport to the Golgi apparatus or delivery to the lysosome. Here Chaumet et al.describe a population of vesicles that can fuse directly with the outer nuclear membrane and deliver cargo into the nuclear envelope, where it can be translocated into the nucleoplasm.

    • Alexandre Chaumet
    • , Graham D. Wright
    •  & Frederic Bard
  • Article
    | Open Access

    Eukaryotic ribosomal proteins contain nuclear localization signals (NLSs) that their bacterial counterparts lack. Here the authors compare homologous proteins from bacterial and eukaryotic ribosomes to show how NLSs could emerge in the course of evolution, and use this knowledge to identify novel NLSs.

    • Sergey Melnikov
    • , Adam Ben-Shem
    •  & Marat Yusupov