Autoantigen Golgin-97, an effector of Arl1 GTPase, participates in traffic from the endosome to the trans-golgi network.
AuthorsLu L, Tai G, Hong W
JournalMol Biol Cell
PubMed ID15269279
'The precise cellular function of Arl1 and its effectors, the GRIP domain Golgins, is not resolved, despite our recent understanding that Arl1 regulates the membrane recruitment of these Golgins. In this report, we describe our functional study of Golgin-97. Using a Shiga toxin B fragment (STxB)-based in vitro transport assay, ... More
Caveolin regulates endocytosis of the muscle repair protein, dysferlin.
AuthorsHernández-Deviez DJ, Howes MT, Laval SH, Bushby K, Hancock JF, Parton RG,
JournalJ Biol Chem
PubMed ID18096699
'Dysferlin and Caveolin-3 are plasma membrane proteins associated with muscular dystrophy. Patients with mutations in the CAV3 gene show dysferlin mislocalization in muscle cells. By utilizing caveolin-null cells, expression of caveolin mutants, and different mutants of dysferlin, we have dissected the site of action of caveolin with respect to dysferlin ... More
AuthorsGaus K, Le Lay S, Balasubramanian N, Schwartz MA
JournalJ Cell Biol
PubMed ID16943184
'The properties of cholesterol-dependent domains (lipid rafts) in cell membranes have been controversial. Because integrin-mediated cell adhesion and caveolin both regulate trafficking of raft components, we investigated the effects of adhesion and caveolin on membrane order. The fluorescent probe Laurdan and two-photon microscopy revealed that focal adhesions are highly ordered; ... More
Metastatic potential of mouse Lewis lung cancer cells is regulated via ganglioside GM1 by modulating the matrix metalloprotease-9 localization in lipid rafts.
AuthorsZhang Q, Furukawa K, Chen HH, Sakakibara T, Urano T, Furukawa K
JournalJ Biol Chem
PubMed ID16636068
'To analyze mechanisms for cancer metastasis, we established high metastatic sublines from mouse Lewis lung cancer (P29) by repeated injection. Sublines established from the two subclones H7 and C4 commonly exhibited increased proliferation and invasion activity and reduced expression of ganglioside GM1, although they showed different preferences in their target ... More
Quantitative and dynamic assessment of the contribution of the ER to phagosome formation.
AuthorsTouret N, Paroutis P, Terebiznik M, Harrison RE, Trombetta S, Pypaert M, Chow A, Jiang A, Shaw J, Yip C, Moore HP, van der Wel N, Houben D, Peters PJ, de Chastellier C, Mellman I, Grinstein S,
JournalCell
PubMed ID16213220
'Phagosomes were traditionally thought to originate from an invagination and scission of the plasma membrane to form a distinct intracellular vacuole. An alternative model implicating the endoplasmic reticulum (ER) as a major component of nascent and maturing phagosomes was recently proposed (Gagnon et al., 2002). To reconcile these seemingly disparate ... More
Modulation of bulbospinal rostral ventral lateral medulla neurons by hypoxia/hypercapnia but not medullary respiratory activity.
AuthorsBoychuk CR, Woerman AL, Mendelowitz D,
JournalHypertension
PubMed ID23108653
'Although sympathetic vasomotor discharge has respiratory modulation, the site(s) responsible for this cardiorespiratory interaction is unknown. One likely source for this coupling is the rostral ventral lateral medulla (RVLM), where presympathetic neurons originate in close apposition to respiratory neurons. The current study tested the hypothesis that RVLM bulbospinal neurons are ... More
Raft composition at physiological temperature and pH in the absence of detergents.
AuthorsAyuyan AG, Cohen FS,
JournalBiophys J
PubMed ID17993486
'Biological rafts were identified and isolated at 37 degrees C and neutral pH. The strategy for isolating rafts utilized membrane tension to generate large domains. For lipid compositions that led only to microscropically unresolvable rafts in lipid bilayers, membrane tension led to the appearance of large, observable rafts. The large ... More
Acute and chronic changes in cholesterol modulate Na-Pi cotransport activity in OK cells.
AuthorsBreusegem SY, Halaihel N, Inoue M, Zajicek H, Lederer E, Barry NP, Sorribas V, Levi M
JournalAm J Physiol Renal Physiol
PubMed ID15769937
'We previously showed an inverse correlation between membrane cholesterol content and Na-P(i) cotransport activity during the aging process and adaptation to alterations in dietary P(i) in the rat (Levi M, Jameson DM, and van der Meer BW. Am J Physiol Renal Fluid Electrolyte Physiol 256: F85-F94, 1989). The purpose of ... More
Correlated fluorescence-atomic force microscopy of membrane domains: structure of fluorescence probes determines lipid localization.
AuthorsShaw JE, Epand RF, Epand RM, Li Z, Bittman R, Yip CM
JournalBiophys J
PubMed ID16361347
'Coupling atomic force microscopy (AFM) with high-resolution fluorescence microscopy is an attractive means of identifying membrane domains by both physical topography and fluorescence. We have used this approach to study the ability of a suite of fluorescent molecules to probe domain structures in supported planar bilayers. These included BODIPY-labeled ganglioside, ... More
Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors.
'CD8+ T cells can mediate eradication of established tumors, and strategies to amplify tumor-reactive T-cell numbers by immunization or ex vivo expansion followed by adoptive transfer are currently being explored in individuals with cancer. Generating effective CD8+ T cell-mediated responses to tumors is often impeded by T-cell tolerance to relevant ... More
Tracing from fat tissue, liver, and pancreas: a neuroanatomical framework for the role of the brain in type 2 diabetes.
AuthorsKreier F, Kap YS, Mettenleiter TC, van Heijningen C, van der Vliet J, Kalsbeek A, Sauerwein HP, Fliers E, Romijn JA, Buijs RM
JournalEndocrinology
PubMed ID16339209
'The hypothalamus uses hormones and the autonomic nervous system to balance energy fluxes in the body. Here we show that the autonomic nervous system has a distinct organization in different body compartments. The same neurons control intraabdominal organs (intraabdominal fat, liver, and pancreas), whereas sc adipose tissue located outside the ... More
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals.
AuthorsDuewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E,
JournalNature
PubMed ID20428172
The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation. Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance ... More
Cytoskeletal control of CD36 diffusion promotes its receptor and signaling function.
The mechanisms that govern receptor coalescence into functional clusters--often a critical step in their stimulation by ligand--are poorly understood. We used single-molecule tracking to investigate the dynamics of CD36, a clustering-responsive receptor that mediates oxidized LDL uptake by macrophages. We found that CD36 motion in the membrane was spatially structured ... More
Specific RNA binding to ordered phospholipid bilayers.
AuthorsJanas T, Janas T, Yarus M,
JournalNucleic Acids Res
PubMed ID16641318
We have studied RNA binding to vesicles bounded by ordered and disordered phospholipid membranes. A positive correlation exists between bilayer order and RNA affinity. In particular, structure-dependent RNA binding appears for rafted (liquid-ordered) domains in sphingomyelin-cholesterol-1,2-dioleoyl-sn-glycero-3-phosphocholine vesicles. Binding to more highly ordered gel phase membranes is stronger, but much less ... More
A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale.
AuthorsBohland JW, Wu C, Barbas H, Bokil H, Bota M, Breiter HC, Cline HT, Doyle JC, Freed PJ, Greenspan RJ, Haber SN, Hawrylycz M, Herrera DG, Hilgetag CC, Huang ZJ, Jones A, Jones EG, Karten HJ, Kleinfeld D, Kötter R, Lester HA, Lin JM, Mensh BD, Mikula S, Panksepp J, Price JL, Safdieh J, Saper CB, Schiff ND, Schmahmann JD, Stillman BW, Svoboda K, Swanson LW, Toga AW, Van Essen DC, Watson JD, Mitra PP,
JournalPLoS Comput Biol
PubMed ID19325892
In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale ... More
Rac-mediated macropinocytosis is a critical route for naked plasmid DNA transfer in mice.
AuthorsFumoto S, Nishi J, Ishii H, Wang X, Miyamoto H, Yoshikawa N, Nakashima M, Nakamura J, Nishida K,
JournalMol Pharm
PubMed ID19492848
We have recently discovered the potential for in vivo naked plasmid DNA (pDNA) transfer into gastric serosal surface cells in mice. As pDNA are huge molecules, the mechanism of gene transfer without carriers and physical forces is of great biological interest. The endocytic route for naked pDNA transfer into gastric ... More
Ca2+-activated IK1 channels associate with lipid rafts upon cell swelling and mediate volume recovery.
AuthorsBarfod ET, Moore AL, Roe MW, Lidofsky SD
JournalJ Biol Chem
PubMed ID17264085
Restoration of cell volume in the continued presence of osmotic stimuli is essential, particularly in hepatocytes, which swell upon nutrient uptake. Responses to swelling involve the Ca2+-dependent activation of K+ channels, which promote fluid efflux to drive volume recovery; however, the channels involved in hepatocellular volume regulation have not been ... More
Glycosphingolipid-facilitated membrane insertion and internalization of cobra cardiotoxin. The sulfatide.cardiotoxin complex structure in a membrane-like environment suggests a lipid-dependent cell-penetrating mechanism for membrane binding polypeptides.
AuthorsWang CH, Liu JH, Lee SC, Hsiao CD, Wu WG
JournalJ Biol Chem
PubMed ID16263708
Cobra cardiotoxins, a family of basic polypeptides having lipid- and heparin-binding capacities similar to the cell-penetrating peptides, induce severe tissue necrosis and systolic heart arrest in snakebite victims. Whereas cardiotoxins are specifically retained on the cell surface via heparan sulfate-mediated processes, their lipid binding ability appears to be responsible, at ... More
Operant conditioning paradigm for juxtacellular recordings in functionally identified cortical neurons during motor execution in head-fixed rats.
AuthorsSantana-Chávez G, Rodriguez-Moreno P, López-Hidalgo M, Olivares-Moreno R, Moreno-López Y, Rojas-Piloni G
JournalJ Neurosci Methods
PubMed ID31669337
'Understanding the configuration of neural circuits and the specific role of distinct cortical neuron types involved in behavior, requires the study of structure-function and connectivity relationships with single cell resolution in awake behaving animals. Despite head-fixed behaving rats have been used for in vivo measuring of neuronal activity, it is ... More
Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition.
AuthorsSeven YB, Simon AK, Sajjadi E, Zwick A, Satriotomo I, Mitchell GS
JournalExp Neurol
PubMed ID31629857
'Respiratory motor neuron survival is critical for maintenance of adequate ventilation and airway clearance, preventing dependence to mechanical ventilation and respiratory tract infections. Phrenic motor neurons are highly vulnerable in rodent models of motor neuron disease versus accessory inspiratory motor pools (e.g. intercostals, scalenus). Thus, strategies that promote phrenic motor ... More
Interference with SRF expression in skeletal muscles reduces peripheral nerve regeneration in mice.
AuthorsWanner R, Knöll B
JournalSci Rep
PubMed ID32210317
Traumatic injury of peripheral nerves typically also damages nerve surrounding tissue including muscles. Hence, molecular and cellular interactions of neighboring damaged tissues might be decisive for successful axonal regeneration of injured nerves. So far, the contribution of muscles and muscle-derived molecules to peripheral nerve regeneration has only poorly been studied. ... More
Novel Drug Candidates Improve Ganglioside Accumulation and Neural Dysfunction in GM1 Gangliosidosis Models with Autophagy Activation.
AuthorsKajihara R, Numakawa T, Odaka H, Yaginuma Y, Fusaki N, Okumiya T, Furuya H, Inui S, Era T
JournalStem Cell Reports
PubMed ID32302553
GM1 gangliosidosis is a lysosomal storage disease caused by loss of lysosomal ß-galactosidase activity and characterized by progressive neurodegeneration due to massive accumulation of GM1 ganglioside in the brain. Here, we generated induced pluripotent stem cells (iPSCs) derived from patients with GM1 gangliosidosis, and the resultant neurons showed impaired neurotransmitter ... More
Deleterious Effect of NMDA Plus Kainate on the Inner Retinal Cells and Ganglion Cell Projection of the Mouse.
AuthorsCalvo E, Milla-Navarro S, Ortuño-Lizarán I, Gómez-Vicente V, Cuenca N, De la Villa P, Germain F
JournalInt J Mol Sci
PubMed ID32106602
Combined administration of N-Methyl-D-Aspartate (NMDA) and kainic acid (KA) on the inner retina was studied as a model of excitotoxicity. The right eye of C57BL6J mice was injected with 1 µL of PBS containing NMDA 30 mM and KA 10 mM. Only PBS was injected in the left eye. One ... More
The Fusarium mycotoxin, 2-Amino-14,16-dimethyloctadecan-3-ol (AOD) induces vacuolization in HepG2 cells.
The mycotoxin 2-Amino-14,16-dimethyloctadecan-3-ol (AOD) has been isolated from cultures of the fungus Fusarium avenaceum, one of the most prevalent Fusarium species. AOD is an analogue of sphinganine and 1-deoxysphinganine, important intermediates in the de novo biosynthesis of cellular sphingolipids. Here we studied cellular effects of AOD using the human liver ... More
Hippocampal Ripple Coordinates Retrosplenial Inhibitory Neurons during Slow-Wave Sleep.
AuthorsOpalka AN, Huang WQ, Liu J, Liang H, Wang DV
JournalCell Rep
PubMed ID31940487
The hippocampus and retrosplenial cortex (RSC) play indispensable roles in memory formation, and importantly, a hippocampal oscillation known as ripple is key to consolidation of new memories. However, it remains unclear how the hippocampus and RSC communicate and the role of ripple oscillation in coordinating the activity between these two ... More
CRMP2 mediates Sema3F-dependent axon pruning and dendritic spine remodeling.
AuthorsZiak J, Weissova R, Jerábková K, Janikova M, Maimon R, Petrasek T, Pukajova B, Kleisnerova M, Wang M, Brill MS, Kasparek P, Zhou X, Alvarez-Bolado G, Sedlacek R, Misgeld T, Stuchlik A, Perlson E, Balastik M
JournalEMBO Rep
PubMed ID31919978
Regulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins are key to the development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to regulate axon guidance by mediating semaphorin 3A (Sema3A) signaling; however, nothing is known about its role in synapse pruning. ... More
Traffic-related air pollutants (TRAP-PM) promote neuronal amyloidogenesis through oxidative damage to lipid rafts.
AuthorsCacciottolo M, Morgan TE, Saffari AA, Shirmohammadi F, Forman HJ, Sioutas C, Finch CE
JournalFree Radic Biol Med
PubMed ID31883973
Traffic-related air pollution particulate matter (TRAP-PM) is associated with increased risk of Alzheimer Disease (AD). Rodent models respond to nano-sized TRAP-PM (nPM) with increased production of amyloid Aß peptides, concurrently with oxidative damage. Because pro-Aß processing of the amyloid precursor protein (APP) occurs on subcellular lipid rafts, we hypothesized that ... More