CKAP4 Regulates Cell Migration via the Interaction with and Recycling of Integrin.
AuthorsOsugi Y, Fumoto K, Kikuchi A
JournalMol Cell Biol
PubMed ID31160493
'Cytoskeleton-associated protein 4 (CKAP4) is an endoplasmic reticulum protein that is also present in the cell surface membrane, where it acts as a receptor for Dickkopf1 (DKK1). In this study, we found that CKAP4 interacts with ß1 integrin and controls the recycling of a5ß1 integrin independently of DKK1. In S2-CP8 ... More
Membrane-bound Gaussia luciferase as a tool to track shedding of membrane proteins from the surface of extracellular vesicles.
AuthorsZaborowski MP, Cheah PS, Zhang X, Bushko I, Lee K, Sammarco A, Zappulli V, Maas SLN, Allen RM, Rumde P, György B, Aufiero M, Schweiger MW, Lai CP, Weissleder R, Lee H, Vickers KC, Tannous BA, Breakefield XO
JournalSci Rep
PubMed ID31758005
'Extracellular vesicles (EVs) released by cells play a role in intercellular communication. Reporter and targeting proteins can be modified and exposed on the surface of EVs to investigate their half-life and biodistribution. A characterization of membrane-bound Gaussia luciferase (mbGluc) revealed that its signal was detected also in a form smaller ... More
Proteomic atlas of organ vasculopathies triggered by Staphylococcus aureus sepsis.
AuthorsToledo AG, Golden G, Campos AR, Cuello H, Sorrentino J, Lewis N, Varki N, Nizet V, Smith JW, Esko JD
JournalNat Commun
PubMed ID31604940
'Sepsis is a life-threatening condition triggered by a dysregulated host response to microbial infection resulting in vascular dysfunction, organ failure and death. Here we provide a semi-quantitative atlas of the murine vascular cell-surface proteome at the organ level, and how it changes during sepsis. Using in vivo chemical labeling and ... More
Investigation of pre-existing reactivity to biotherapeutics can uncover potential immunogenic epitopes and predict immunogenicity risk.
AuthorsBivi N, Moore T, Rodgers G, Denning H, Shockley T, Swearingen CA, Gelfanova V, Calderon B, Peterson DA, Hodsdon ME, Siegel RW, Higgs RE, Konrad RJ
JournalMAbs
PubMed ID31099718
'Despite recent advances in the development of tools to predict immunogenicity risk of biotherapeutic molecules, the ability of a protein to elicit the formation of anti-drug antibodies (ADA) remains one of the most common causes for termination of clinical development programs. In this study, we use ADA assays to detect ... More
Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood-brain barrier and blood-retina barrier development and maintenance.
AuthorsWang Y, Cho C, Williams J, Smallwood PM, Zhang C, Junge HJ, Nathans J
JournalProc Natl Acad Sci U S A
PubMed ID30478038
'ß-Catenin signaling controls the development and maintenance of the blood-brain barrier (BBB) and the blood-retina barrier (BRB), but the division of labor and degree of redundancy between the two principal ligand-receptor systems-the Norrin and Wnt7a/Wnt7b systems-are incompletely defined. Here, we present a loss-of-function genetic analysis of postnatal BBB and BRB ... More
Beneficial Role of Rosuvastatin in Blood-Brain Barrier Damage Following Experimental Ischemic Stroke.
'Hemorrhage transformation is the most challenging preventable complication in thrombolytic therapy and is related to recombinant tissue plasminogen activator (rt-PA)-induced blood-brain barrier (BBB) damage. Intraperitoneal injections of normal or high doses of rosuvastatin were administered to Balb/c mice 20 min prior to middle cerebral artery occlusion (MCAO) surgery for 3 ... More
Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody.
AuthorsSchommers P, Gruell H, Abernathy ME, Tran MK, Dingens AS, Gristick HB, Barnes CO, Schoofs T, Schlotz M, Vanshylla K, Kreer C, Weiland D, Holtick U, Scheid C, Valter MM, van Gils MJ, Sanders RW, Vehreschild JJ, Cornely OA, Lehmann C, Fätkenheuer G, Seaman MS, Bloom JD, Bjorkman PJ, Klein F
JournalCell
PubMed ID32004464
'Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V' ... More
Severe, but not mild heat-shock treatment induces immunogenic cell death in cancer cells.
AuthorsAdkins I, Sadilkova L, Hradilova N, Tomala J, Kovar M, Spisek R
JournalOncoimmunology
PubMed ID28638734
The mechanisms of immunogenicity underlying mild heat-shock (mHS) treatment < 42°C of tumor cells are largely attributed to the action of heat-shock proteins; however, little is known about the immunogenicity of tumor cells undergoing severe cytotoxic heat-shock treatment (sHS > 43°C). Here, we found that sHS, but not mHS (42°C), ... More
Mechanotransduction by PCDH15 Relies on a Novel cis-Dimeric Architecture.
AuthorsDionne G, Qiu X, Rapp M, Liang X, Zhao B, Peng G, Katsamba PS, Ahlsen G, Rubinstein R, Potter CS, Carragher B, Honig B, Müller U, Shapiro L
JournalNeuron
PubMed ID30057206
The tip link, a filament formed by protocadherin 15 (PCDH15) and cadherin 23, conveys mechanical force from sound waves and head movement to open hair-cell mechanotransduction channels. Tip-link cadherins are thought to have acquired structural features critical for their role in mechanotransduction. Here, we biophysically and structurally characterize the unusual cis-homodimeric ... More
The Capsule of Cryptococcus neoformans Modulates Phagosomal pH through Its Acid-Base Properties.
AuthorsDe Leon-Rodriguez CM, Fu MS, Çorbali MO, Cordero RJB, Casadevall A
JournalmSphere
PubMed ID30355667
Phagosomal acidification is a critical cellular mechanism for the inhibition and killing of ingested microbes by phagocytic cells. The acidic environment activates microbicidal proteins and creates an unfavorable environment for the growth of many microbes. Consequently, numerous pathogenic microbes have developed strategies for countering phagosomal acidification through various mechanisms that ... More
Endosomal signalling via exosome surface TGFß-1.
AuthorsShelke GV, Yin Y, Jang SC, Lässer C, Wennmalm S, Hoffmann HJ, Li L, Gho YS, Nilsson JA, Lötvall J
JournalJ Extracell Vesicles
PubMed ID31595182
Extracellular vesicles such as exosomes convey biological messages between cells, either by surface-to-surface interaction or by shuttling of bioactive molecules to a recipient cell's cytoplasm. Here we show that exosomes released by mast cells harbour both active and latent transforming growth factor ß-1 (TGFß-1) on their surfaces. The latent form ... More
Engineering of anti-human interleukin-4 receptor alpha antibodies with potent antagonistic activity.
AuthorsKim JE, Jung K, Kim JA, Kim SH, Park HS, Kim YS
JournalSci Rep
PubMed ID31123339
Development of antagonistic antibody (Ab) against interleukin-4 receptor alpha (IL-4Ra) subunit of IL-4/IL-13 receptors is a promising therapeutic strategy for T helper 2 (T
Diabetes mellitus (DM) significantly increases susceptibility to central nervous system (CNS) pathologies, including stroke, vascular dementia, cognitive deficits and Alzheimer's disease. Previous studies (mostly using the streptozotocin model) suggested that blood-brain barrier (BBB) disruption is involved in these conditions. Here, we examined the integrity of brain capillaries and BBB permeability ... More
Sex-regulated gene dosage effect of PPARa on synaptic plasticity.
AuthorsPierrot N, Ris L, Stancu IC, Doshina A, Ribeiro F, Tyteca D, Baugé E, Lalloyer F, Malong L, Schakman O, Leroy K, Kienlen-Campard P, Gailly P, Brion JP, Dewachter I, Staels B, Octave JN
JournalLife Sci Alliance
PubMed ID30894406
Mechanisms driving cognitive improvements following nuclear receptor activation are poorly understood. The peroxisome proliferator-activated nuclear receptor alpha (PPARa) forms heterodimers with the nuclear retinoid X receptor (RXR). We report that PPARa mediates the improvement of hippocampal synaptic plasticity upon RXR activation in a transgenic mouse model with cognitive deficits. This ... More
Beta-catenin signaling regulates barrier-specific gene expression in circumventricular organ and ocular vasculatures.
AuthorsWang Y, Sabbagh MF, Gu X, Rattner A, Williams J, Nathans J
JournalElife
PubMed ID30932813
The brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum and parenchyma, a property that defines the blood-brain and blood-retina barriers. Exceptions to this pattern are found in circumventricular organs (CVOs), small midline brain structures that are supplied by high ... More
Protein diaphanous homolog 1 (Diaph1) promotes myofibroblastic activation of hepatic stellate cells by regulating Rab5a activity and TGFß receptor endocytosis.
AuthorsLiu D, Fu X, Wang Y, Wang X, Wang H, Wen J, Kang N
JournalFASEB J
PubMed ID32304339
TGFß induces the differentiation of hepatic stellate cells (HSCs) into tumor-promoting myofibroblasts but underlying mechanisms remain incompletely understood. Because endocytosis of TGFß receptor II (TßRII), in response to TGFß stimulation, is a prerequisite for TGF signaling, we investigated the role of protein diaphanous homolog 1 (known as Diaph1 or mDia1) ... More
Focal Adhesion Kinase Promotes Hepatic Stellate Cell Activation by Regulating Plasma Membrane Localization of TGFß Receptor 2.
AuthorsChen Y, Li Q, Tu K, Wang Y, Wang X, Liu D, Chen C, Liu D, Yang R, Qiu W, Kang N
JournalHepatol Commun
PubMed ID32025610
Transforming growth factor ß (TGFß) induces hepatic stellate cell (HSC) differentiation into tumor-promoting myofibroblast, although underlying mechanism remains incompletely understood. Focal adhesion kinase (FAK) is activated in response to TGFß stimulation, so it transmits TGFß stimulus to extracellular signal-regulated kinase and P38 mitogen-activated protein kinase signaling. However, it is unknown ... More
Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome.
AuthorsLi M, Nishio SY, Naruse C, Riddell M, Sapski S, Katsuno T, Hikita T, Mizapourshafiyi F, Smith FM, Cooper LT, Lee MG, Asano M, Boettger T, Krueger M, Wietelmann A, Graumann J, Day BW, Boyd AW, Offermanns S, Kitajiri SI, Usami SI, Nakayama M
JournalNat Commun
PubMed ID32165640
Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This ... More