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Journal of Cell Science

Lauriane Mas, Adeline Cieren, Christian Delphin, Agnès Journet, Laurence Aubry
Arrestins are key adaptor proteins that control the fate of cell-surface membrane proteins and modulate downstream signaling cascades. Dictyostelium discoideum genome encodes six arrestin-related proteins, harboring additional modules besides the arrestin domain. Here, we studied AdcB and AdcC, two homologs that contain C2 and SAM-domains. We showed that AdcC, in contrast to AdcB, responds to various stimuli (such as the chemoattractants cAMP and folate) known to induce a cytosolic calcium rise by a transient translocation to the plasma membrane and that calcium is a direct regulator of AdcC localization...
September 12, 2018: Journal of Cell Science
Edward Jenkins, Ana Mafalda Santos, Caitlin O'Brien-Ball, James H Felce, Martin J Wilcock, Deborah Hatherley, Michael L Dustin, Simon J Davis, Christian Eggeling, Erdinc Sezgin
The spatiotemporal regulation of signalling proteins at the contacts formed between immune cells and their targets determines how and when immune responses begin and end. Therapeutic control of immune responses will therefore rely on thorough elucidation of the molecular processes occurring at these interfaces. However, the detailed investigation of each component's contribution to the formation and regulation of the contact is hampered by the complexities of cell composition and architecture. Moreover, the transient nature of these interactions creates additional challenges, especially for using advanced imaging technology...
September 12, 2018: Journal of Cell Science
Brian Belardi, Sungmin Son, Michael D Vahey, Jinzhi Wang, Jianghui Hou, Daniel A Fletcher
Tight junctions have been hypothesized to act as molecular fences in the plasma membrane of epithelial cells, helping to form differentiated apical and basolateral domains. While this fence function is believed to arise from the interaction of four-pass transmembrane claudins, the complexity of tight junctions has made direct evidence of their role as a putative diffusion barrier difficult to obtain. Here we address this challenge by reconstituting claudin-4 into giant unilamellar vesicles using microfluidic jetting...
September 12, 2018: Journal of Cell Science
Yoshitaka Fujihara, Asami Oji, Kanako Kojima-Kita, Tamara Larasati, Masahito Ikawa
Chemokines are signaling proteins that are secreted to induce chemotaxis during immunological events. However, the functions of transmembrane-type chemokine-like factor (CKLF) and the protein family CMTM (CKLF-like MARVEL transmembrane domain containing) remain to be determined. In this study, we focused on the testis-specific mouse Cmtm gene cluster ( Cmtm1 , Cmtm2a , and Cmtm2b ) and generated CRISPR/Cas9-mediated mutant mice to examine its physiological functions. Although Cmtm1 mutant mice were fertile, Cmtm2a and Cmtm2b double mutant mice had defects in male fertility due to impaired sperm function...
September 12, 2018: Journal of Cell Science
Seng Zhu, Shaarvari Bhat, Sylvie Syan, Yoshihiko Kuchitsu, Mitsunori Fukuda, Chiara Zurzolo
Tunneling nanotubes (TNTs) are actin-enriched membranous channels enabling cells to communicate over long distances. TNT-like structures form between various cell types and mediate the exchange of different cargos, such as ions, vesicles, organelles, and pathogens. Thus, they may play a role in physiological conditions and diseases (e.g., cancer and infection). TNTs also allow the intercellular passage of protein aggregates related to neurodegenerative diseases, thus propagating protein misfolding. Understanding the mechanism of TNT formation is mandatory to reveal the mechanism of disease propagation and to uncover their physiological function...
September 12, 2018: Journal of Cell Science
Ferheen Abbasi, Haruhiko Miyata, Keisuke Shimada, Akane Morohoshi, Kaori Nozawa, Takafumi Matsumura, Zoulan Xu, Putri Pratiwi, Masahito Ikawa
The flagellum is an evolutionarily conserved appendage used for sensing and locomotion. Its backbone is the axoneme and a component of the axoneme is the radial spoke (RS), a protein complex implicated in flagellar motility regulation. Numerous diseases occur if the axoneme is improperly formed, such as primary ciliary dyskinesia (PCD) and infertility. RSPH6A is an ortholog of Chlamydomonas RSP6 in the RS head and is evolutionarily conserved. While some RS head proteins have been linked to PCD, little is known about RSPH6A...
September 5, 2018: Journal of Cell Science
Lucas C Reineke, Shebna A Cheema, Julien Dubrulle, Joel R Neilson
Stress granules (SGs) assemble under stress-induced conditions that inhibit protein synthesis, including phosphorylation of eIF2α, inhibition of the RNA helicase eIF4a, or inactivation of mTORC1. Classically defined stress granules are composed of translation initiation factors, 40S ribosomes, RNA binding proteins, and poly(A)+ mRNAs. As such, they represent an important compartment for storage of mRNAs and regulation of their translation. Emerging work on SGs indicates that these structures may promote cellular survival in diverse disease states...
September 5, 2018: Journal of Cell Science
Zane J Bergman, Jonathan Wong, David G Drubin, Georjana Barnes
Microtubules (MTs) are important for cellular structure, transport of cargoes, and segregation of chromosomes and organelles during mitosis. The stochastic growth and shrinkage of MTs, known as dynamic instability, is necessary for these functions. Previous studies to determine how individual MT-associated proteins (MAPs) affect MT dynamics have been performed either through in vivo studies, which provide limited opportunity for observation of individual MTs or manipulation of conditions, or in vitro studies, which either focus on purified proteins, and therefore lack cellular complexity, or on cell extracts made from genetically intractable organisms...
September 5, 2018: Journal of Cell Science
Charlotte M de Winde, Alexandra L Matthews, Sjoerd van Deventer, Alie van der Schaaf, Neil D Tomlinson, Erik Jansen, Johannes A Eble, Bernhard Nieswandt, Helen M McGettrick, Carl G Figdor, Michael G Tomlinson, Sophie E Acton, Annemiek B van Spriel
Cell migration is central to evoke a potent immune response. Dendritic cell (DC) migration to lymph nodes is dependent on the interaction of C-type lectin-like receptor 2 (CLEC-2) expressed by DCs with podoplanin expressed by lymph node stromal cells, although the molecular mechanisms remain elusive. Here, we show that CLEC-2-dependent DC migration is controlled by tetraspanin CD37, a membrane-organizing protein. We identified a specific interaction between CLEC-2 and CD37, and myeloid cells lacking CD37 ( Cd37-/- ) expressed reduced surface CLEC-2...
September 5, 2018: Journal of Cell Science
Bhagawat C Subramanian, Konstadinos Moissoglu, Carole A Parent
Neutrophils sense and respond to diverse chemotactic cues using G-protein coupled receptors (GPCRs). However, the precise trafficking dynamics of chemoattractant GPCRs during neutrophil activation and chemotaxis remain unclear. Here, using small molecule inhibitors and CRISPR-based knockouts, we establish that two primary chemoattractant GPCRs - formyl peptide receptor 1 (FPR1) and C5a receptor 1 (C5aR) - internalize in a CDC42-Actin-dependent manner. Using live-cell imaging, we demonstrate that upon stimulation FPR1 rapidly clusters, re-distributes along the plasma membrane to the trailing edge, where it internalizes and is directionally trafficked towards the front of migrating primary human neutrophils...
August 29, 2018: Journal of Cell Science
Maximilien Courgeon, DanQing He, Hui Hua Liu, Kevin Legent, Jessica E Treisman
Mammalian members of the ErbB family, including the Epidermal Growth Factor Receptor (EGFR), can regulate transcription, DNA replication and repair through nuclear entry of either the full-length proteins or their cleaved cytoplasmic domains. In cancer cells, these nuclear functions contribute to tumor progression and drug resistance. We examined whether the single Drosophila EGFR can also localize to the nucleus. A chimeric EGFR protein fused at its cytoplasmic C-terminus to DNA-binding and transcriptional activation domains strongly activated transcriptional reporters when overexpressed in cultured cells or in vivo...
August 29, 2018: Journal of Cell Science
Linda Sutherland, Madeleine Ruhe, Daniela Gattegno-Ho, Karanjit Mann, Jennifer Greaves, Magdalena Koscielniak, Stephen Meek, Zen Lu, Martin Waterfall, Ryan Taylor, Anestis Tsakiridis, Helen Brown, Sutherland K Maciver, Anagha Joshi, Michael Clinton, Luke H Chamberlain, Austin Smith, Tom Burdon
The cytokine leukaemia Inhibitory factor (LIF) promotes self-renewal of mouse embryonic stem cells (ESC) through activation of the transcription factor Stat3. However, the contribution of other ancillary pathways stimulated by LIF in ESCs, such as the MAPK and PI3K pathways, is less well understood. We show here that naïve-type mouse ESCs express high levels of a novel effector of the MAPK and PI3K pathways. This effector is an isoform of the Gab1 (Grb2-associated binder protein 1) adaptor protein that lacks the N-terminal Pleckstrin Homology (PH) membrane-binding domain...
August 28, 2018: Journal of Cell Science
Angela Rubio, Natalia García-Blanco, Alicia Vázquez-Bolado, María Belén Suárez, Sergio Moreno
In Nature, cells and in particular unicellular microorganisms are exposed to a variety of nutritional environments. Fission yeast cells cultured in nitrogen-rich media grow fast, divide with a large size and show a short G1 and a long G2. However, when they are cultured in nitrogen-poor media they reduce the growth rate and cell size and show a long G1 and a short G2. In this study, we have compared the phenotypes of cells lacking the highly conserved Cdk inhibitor Rum1 and the APC/C activator Ste9 in nitrogen-rich and nitrogen-poor media...
August 28, 2018: Journal of Cell Science
Patrick C Cunningham, Katherine Waldeck, Barry Ganetzky, Daniel T Babcock
Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons, resulting in progressive locomotor dysfunction. Identification of genes required for the maintenance of these neurons should help to identify potential therapeutic targets. However, little is known regarding the factors that render dopaminergic neurons selectively vulnerable to PD. Here we show that Drosophila melanogaster scarlet mutants exhibit an age-dependent progressive loss of dopaminergic neurons, along with subsequent locomotor defects and a shortened lifespan...
August 28, 2018: Journal of Cell Science
Sudeshna Nag, Shikha Rani, Sarmistha Mahanty, Christin Bissig, Pooja Arora, Cristina Azevedo, Adolfo Saiardi, Peter van der Sluijs, Cedric Delevoye, Guillaume van Niel, Graca Raposo, Subba Rao Setty
Sorting endosomes (SEs) are the regulatory hubs for sorting cargo to multiple organelles, including lysosome-related organelles such as melanosomes in melanocytes. In parallel, melanosome biogenesis is initiated from SEs with the processing and sequential transport of melanocyte-specific proteins toward maturing melanosomes. However, the mechanism of cargo segregation on SEs is largely unknown. RNAi screening in melanocytes revealed that knockdown of Rab4A results in defective melanosome maturation. Rab4A-depletion increases vacuolar endosomes and disturbs the cargo sorting, which in turn lead to the mislocalization of melanosomal proteins to lysosomes, cell surface and exosomes...
August 28, 2018: Journal of Cell Science
Hannah E Arbach, Marcus Harland-Dunaway, Jessica K Chang, Andrea E Wills
Changes in nuclear morphology contribute to regulation of complex cell properties, including differentiation and tissue elasticity. Perturbations of nuclear morphology are associated with pathologies that include, progeria, cancer, and muscular dystrophy. The mechanisms governing nuclear shape changes in healthy cells remain poorly understood, partially because there are few healthy models of nuclear shape variation. Here, we introduce nuclear branching in epidermal fin cells of Xenopus tropicalis as a model for extreme variation of nuclear morphology in a diverse population of healthy cells...
August 21, 2018: Journal of Cell Science
Bahtiyar Kurtulmus, Cheng Yuan, Jakob Schuy, Annett Neuner, Shoji Hata, Georgios Kalamakis, Ana Martin-Villalba, G Pereira
Cilia perform essential signalling functions during development and tissue homeostasis. The mother centriole plays a key role during ciliogenesis. The distal appendages of the mother centriole form a platform that docks ciliary vesicles and removes CP110/Cep97 inhibitory complexes from the mother centriole. Here, we analysed the role of LRRC45 in appendage formation and ciliogenesis. We show that the core appendage proteins Cep83 and SCLT1 recruit LRRC45 to the mother centriole. Once there LRRC45 recruits FBF1...
August 21, 2018: Journal of Cell Science
Rini Ravindran, Paula Polk, Lucy C Robinson, Kelly Tatchell
Protein ubiquitylation regulates many cellular processes, including cell division. We report here a novel mutation altering the S. cerevisiae E1 ubiquitin activating enzyme ( uba1-W928R) that suppresses the temperature sensitivity and chromosome loss phenotype of a well-characterized Aurora B mutant ( ip1-2 ). The uba1-W928R mutation increases Histone H3-S10 phosphorylation in the ipl1-2 strain, indicating that uba1-W928R acts by increasing Ipl1 activity and/or reducing the opposing PP1 (Glc7 in S. cerevisiae ) phosphatase activity...
July 27, 2018: Journal of Cell Science
Alexander Buffone, Nicholas R Anderson, Daniel A Hammer
No abstract text is available yet for this article.
September 10, 2018: Journal of Cell Science
Stefanie J Oeding, Katarzyna Majstrowicz, Xiao-Ping Hu, Vera Schwarz, Angelika Freitag, Ulrike Honnert, Petra Nikolaus, Martin Bähler
Mitochondrial distribution in cells is critical for cellular function and proper inheritance during cell division. In mammalian cells, mitochondria are transported predominantly along microtubules by kinesin and dynein motors that bind indirectly via TRAK1 and TRAK2 to outer mitochondrial membrane proteins Miro1 and Miro2 (Miro1/2). Here, using proximity labelling, we identified Miro1/2 as potential binding partners of myosin XIX (Myo19). Interaction studies show that Miro1 binds directly to a C-terminal fragment of the Myo19 tail region and that Miro1/2 recruit the Myo19 tail in vivo This recruitment is regulated by the nucleotide state of the N-terminal Rho-like GTPase domain of Miro1/2...
September 10, 2018: Journal of Cell Science
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