Targeting host mitochondria: A role for the Trypanosoma cruzi amastigote flagellum.
AuthorsLentini G, Dos Santos Pacheco N, Burleigh BA,
JournalCell Microbiol
PubMed ID29119655
'Trypanosoma cruzi is the kinetoplastid protozoan parasite that causes human Chagas disease, a chronic disease with complex outcomes including severe cardiomyopathy and sudden death. In mammalian hosts, T. cruzi colonises a wide range of tissues and cell types where it replicates within the host cell cytoplasm. Like all intracellular pathogens, T. cruzi ... More
Methamphetamine Augments Concurrent Astrocyte Mitochondrial Stress, Oxidative Burden, and Antioxidant Capacity: Tipping the Balance in HIV-Associated Neurodegeneration.
AuthorsBorgmann K, Ghorpade A,
JournalNeurotox Res
PubMed ID28993979
'Methamphetamine (METH) use, with and without human immunodeficiency virus (HIV)-1 comorbidity, exacerbates neurocognitive decline. Oxidative stress is a probable neurotoxic mechanism during HIV-1 central nervous system infection and METH abuse, as viral proteins, antiretroviral therapy and METH have each been shown to induce mitochondrial dysfunction. However, the mechanisms regulating mitochondrial ... More
Increased Fc?RIIB dominance contributes to the emergence of resistance to therapeutic antibodies in chronic lymphocytic leukaemia patients.
AuthorsBurgess M, Mapp S, Mazzieri R, Cheung C, Chambers L, Mattarollo SR, Mollee P, Gill D, Saunders NA
JournalOncogene
PubMed ID27748757
Resistance to therapeutic antibodies in chronic lymphocytic leukaemia (CLL) is common. In this study, we show that therapeutic antibodies against CD62L (CD62L-Ab) or CD20 (obinutuzumab) were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADP) in primary cultures of CLL cells. CLL cells derived from patients with active disease ... More
PI(3,5)P2 biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms.
AuthorsMironova YA, Lenk GM, Lin JP, Lee SJ, Twiss JL, Vaccari I, Bolino A, Havton LA, Min SH, Abrams CS, Shrager P, Meisler MH, Giger RJ
JournalElife
PubMed ID27008179
Proper development of the CNS axon-glia unit requires bi-directional communication between axons and oligodendrocytes (OLs). We show that the signaling lipid phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2] is required in neurons and in OLs for normal CNS myelination. In mice, mutations of Fig4, Pikfyve or Vac14, encoding key components of the PI(3,5)P2 biosynthetic complex, ... More
The endosomal neuronal proteins Nsg1/NEEP21 and Nsg2/P19 are itinerant, not resident proteins of dendritic endosomes.
AuthorsYap CC, Digilio L, McMahon L, Winckler B,
JournalSci Rep
PubMed ID28874679
Membrane traffic critically regulates most aspects of neuronal function. Neurons express many neuronal-specific proteins that regulate membrane traffic, including the poorly understood small transmembrane proteins neural-specific gene 1 and 2 (Nsg1/NEEP21 and Nsg2/P19). Nsg1 has been implicated in regulating endosomal recycling and sorting of several important neuronal receptors. Nsg2 is ... More
Novel ecto-tagged integrins reveal their trafficking in live cells.
Integrins are abundant heterodimeric cell-surface adhesion receptors essential in multicellular organisms. Integrin function is dynamically modulated by endo-exocytic trafficking, however, major mysteries remain about where, when, and how this occurs in living cells. To address this, here we report the generation of functional recombinant ß1 integrins with traceable tags inserted ... More
A functional screening of the kinome identifies the Polo-like kinase 4 as a potential therapeutic target for malignant rhabdoid tumors, and possibly, other embryonal tumors of the brain.
AuthorsSredni ST, Suzuki M, Yang JP, Topczewski J, Bailey AW, Gokirmak T, Gross JN, de Andrade A, Kondo A, Piper DR, Tomita T
JournalPediatr Blood Cancer
PubMed ID28067514
Malignant rhabdoid tumors (MRTs) are deadly embryonal tumors of the infancy. With poor survival and modest response to available therapies, more effective and less toxic treatments are needed. We hypothesized that a systematic screening of the kinome will reveal kinases that drive rhabdoid tumors and can be targeted by specific ... More
Simultaneous Multicolor Single-Molecule Tracking with Single-Laser Excitation via Spectral Imaging.
AuthorsHuang T, Phelps C, Wang J, Lin LJ, Bittel A, Scott Z, Jacques S, Gibbs SL, Gray JW, Nan X,
JournalBiophys J
PubMed ID29401428
Single-molecule tracking (SMT) offers rich information on the dynamics of underlying biological processes, but multicolor SMT has been challenging due to spectral cross talk and a need for multiple laser excitations. Here, we describe a single-molecule spectral imaging approach for live-cell tracking of multiple fluorescent species at once using a ... More
Dynamic Collision Behavior Between Osteoblasts and Tumor Cells Regulates the Disordered Arrangement of Collagen Fiber/Apatite Crystals in Metastasized Bone.
AuthorsMatsugaki A, Harada T, Kimura Y, Sekita A, Nakano T,
JournalInt J Mol Sci
PubMed ID30400633
Bone metastasis is one of the most intractable bone diseases; it is accompanied with a severe mechanical dysfunction of bone tissue. We recently discovered that the disorganized collagen/apatite microstructure in cancer-bearing bone is a dominant determinant of the disruption of bone mechanical function; disordered osteoblast arrangement was found to be ... More
2-Methoxyestradiol Affects Mitochondrial Biogenesis Pathway and Succinate Dehydrogenase Complex Flavoprotein Subunit A in Osteosarcoma Cancer Cells.
AuthorsGorska-Ponikowska M, Kuban-Jankowska A, Eisler SA, Perricone U, Lo Bosco G, Barone G, Nussberger S,
JournalCancer Genomics Proteomics
PubMed ID29275365
Dysregulation of mitochondrial pathways is implicated in several diseases, including cancer. Notably, mitochondrial respiration and mitochondrial biogenesis are favored in some invasive cancer cells, such as osteosarcoma. Hence, the aim of the current work was to investigate the effects of 2-methoxyestradiol (2-ME), a potent anticancer agent, on the mitochondrial biogenesis ... More
Mitochondrially targeted p53 or DBD subdomain is superior to wild type p53 in ovarian cancer cells even with strong dominant negative mutant p53.
AuthorsLu P, Vander Mause ER, Redd Bowman KE, Brown SM, Ahne L, Lim CS,
JournalJ Ovarian Res
PubMed ID31092272
While tumor suppressor p53 functions primarily as a transcription factor in the nucleus, cellular stress can cause p53 to translocate to the mitochondria and directly trigger a rapid apoptotic response. We have previously shown that fusing p53 (or its DNA binding domain, DBD, alone) to the mitochondrial targeting signal (MTS) ... More
Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity.
AuthorsAlexander JM, Guan J, Li B, Maliskova L, Song M, Shen Y, Huang B, Lomvardas S, Weiner OD,
JournalElife
PubMed ID31124784
Enhancers are important regulatory elements that can control gene activity across vast genetic distances. However, the underlying nature of this regulation remains obscured because it has been difficult to observe in living cells. Here, we visualize the spatial organization and transcriptional output of the key pluripotency regulator Sox2 and its ... More
Osteoblastic lysosome plays a central role in mineralization.
Mineralization is the most fundamental process in vertebrates. It is predominantly mediated by osteoblasts, which secrete mineral precursors, most likely through matrix vesicles (MVs). These vesicular structures are calcium and phosphate rich and contain organic material such as acidic proteins. However, it remains largely unknown how intracellular MVs are transported ... More