Rapid identification of highly potent human anti-GPCR antagonist monoclonal antibodies.
AuthorsScott MJ, Jowett A, Orecchia M, Ertl P, Ouro-Gnao L, Ticehurst J, Gower D, Yates J, Poulton K, Harris C, Mullin MJ, Smith KJ, Lewis AP, Barton N, Washburn ML, de Wildt R
Journal
PubMed ID32343620
'Complex cellular targets such as G protein-coupled receptors (GPCRs), ion channels, and other multi-transmembrane proteins represent a significant challenge for therapeutic antibody discovery, primarily because of poor stability of the target protein upon extraction from cell membranes. To assess whether a limited set of membrane-bound antigen formats could be exploited ... More
Potent neutralizing monoclonal antibodies against Ebola virus isolated from vaccinated donors.
AuthorsFan P, Chi X, Liu G, Zhang G, Chen Z, Liu Y, Fang T, Li J, Banadyga L, He S, Yu C, Qiu X, Chen W
Journal
PubMed ID32213108
Ebola virus (EBOV) can cause severe hemorrhagic fever in humans, and no approved treatment is currently available. Although several antibodies have achieved good protection in animal models, the potential emerging isolates of ebolavirus and the unknown effects of experimental antibodies in humans underscore the need to develop additional antibodies to ... More
Junctional and somatic hypermutation-induced CX
AuthorsYi C, Xia J, He L, Ling Z, Wang X, Yan Y, Wang J, Zhao X, Fan W, Sun X, Zhang R, Ye S, Zhang R, Xu Y, Ma L, Zhang Y, Zhou H, Huang Z, Niu J, Long G, Lu J, Zhong J, Sun B
JournalCell Mol Immunol
PubMed ID32235917
'Induction of broadly neutralizing monoclonal antibodies (bNAbs) that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus (HCV) vaccine research. The study of bNAbs arising in natural infection is essential in this endeavor. We generated a human antibody, 8D6, recognizing the E2 protein of HCV ... More
Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions.
AuthorsZhou W, Stanger SJ, Anderson AL, Bernstein IR, De Iuliis GN, McCluskey A, McLaughlin EA, Dun MD, Nixon B
JournalBMC Biol
PubMed ID30999907
'The mammalian epididymis is responsible for the provision of a highly specialized environment in which spermatozoa acquire functional maturity and are subsequently stored in preparation for ejaculation. Making important contributions to both processes are epididymosomes, small extracellular vesicles released from the epididymal soma via an apocrine secretory pathway. While considerable ... More
Molecular determinants in Frizzled, Reck, and Wnt7a for ligand-specific signaling in neurovascular development.
AuthorsCho C, Wang Y, Smallwood PM, Williams J, Nathans J
JournalElife
PubMed ID31225798
'The molecular basis of Wnt-Frizzled specificity is a central question in developmental biology. Reck, a multi-domain and multi-functional glycosylphosphatidylinositol-anchored protein, specifically enhances beta-catenin signaling by Wnt7a and Wnt7b in cooperation with the 7-transmembrane protein Gpr124. Among amino acids that distinguish Wnt7a and Wnt7b from other Wnts, two clusters are essential ... More
Norrin-induced Frizzled4 endocytosis and endo-lysosomal trafficking control retinal angiogenesis and barrier function.
AuthorsZhang C, Lai MB, Khandan L, Lee LA, Chen Z, Junge HJ
JournalNat Commun
PubMed ID28675177
Angiogenesis and blood-brain barrier formation are required for normal central nervous system (CNS) function. Both processes are controlled by Wnt or Norrin (NDP) ligands, Frizzled (FZD) receptors, and ß-catenin-dependent signalling in vascular endothelial cells. In the retina, FZD4 and the ligand NDP are critical mediators of signalling and are mutated ... More
USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A.
AuthorsUckelmann M, Densham RM, Baas R, Winterwerp HHK, Fish A, Sixma TK, Morris JR
JournalNat Commun
PubMed ID29335415
BRCA1-BARD1-catalyzed ubiquitination of histone H2A is an important regulator of the DNA damage response, priming chromatin for repair by homologous recombination. However, no specific deubiquitinating enzymes (DUBs) are known to antagonize this function. Here we identify ubiquitin specific protease-48 (USP48) as a H2A DUB, specific for the C-terminal BRCA1 ubiquitination ... More
The IgCAM CLMP regulates expression of Connexin43 and Connexin45 in intestinal and ureteral smooth muscle contraction in mice.
AuthorsLanghorst H, Jüttner R, Groneberg D, Mohtashamdolatshahi A, Pelz L, Purfürst B, Schmidt-Ott KM, Friebe A, Rathjen FG
JournalDis Model Mech
PubMed ID29361518
CAR-like membrane protein (CLMP), an immunoglobulin cell adhesion molecule (IgCAM), has been implicated in congenital short-bowel syndrome in humans, a condition with high mortality for which there is currently no cure. We therefore studied the function of CLMP in a ... More
Identification of CD36 as a new interaction partner of membrane NEU1: potential implication in the pro-atherogenic effects of the elastin receptor complex.
AuthorsKawecki C, Bocquet O, Schmelzer CEH, Heinz A, Ihling C, Wahart A, Romier B, Bennasroune A, Blaise S, Terryn C, Linton KJ, Martiny L, Duca L, Maurice P
JournalCell Mol Life Sci
PubMed ID30498996
In addition to its critical role in lysosomes for catabolism of sialoglycoconjugates, NEU1 is expressed at the plasma membrane and regulates a myriad of receptors by desialylation, playing a key role in many pathophysiological processes. Here, we developed a proteomic approach dedicated to the purification and identification by LC-MS/MS of ... More
Trafficking of the amino acid transporter B
AuthorsKovalchuk V, Samluk L, Juraszek B, Jurkiewicz-Trzaska D, Sucic S, Freissmuth M, Nalecz KA
An ideal vaccine against HIV-1 will specifically elicit bNAbs (broadly neutralizing antibodies) which can cross-neutralize a wide spectrum of circulating viral strains belonging to different clades. The current paradigm for developing such a vaccine is to generate HIV-1 envelope (Env)-based immunogens which can specifically elicit bNAbs. For this purpose, it ... More
Curcumin Analogue C1 Promotes Hex and Gal Recruitment to the Plasma Membrane via mTORC1-Independent TFEB Activation.
AuthorsMagini A, Polchi A, Di Meo D, Buratta S, Chiaradia E, Germani R, Emiliani C, Tancini B
JournalInt J Mol Sci
PubMed ID30889901
The monocarbonyl analogue of curcumin (1E,4E)-1,5-Bis(2-methoxyphenyl)penta-1,4-dien-3-one (C1) has been used as a specific activator of the master gene transcription factor EB (TFEB) to correlate the activation of this nuclear factor with the increased activity of lysosomal glycohydrolases and their recruitment to the cell surface. The presence of active lysosomal glycohydrolases ... More
Dlg1 activates beta-catenin signaling to regulate retinal angiogenesis and the blood-retina and blood-brain barriers.
AuthorsCho C, Wang Y, Smallwood PM, Williams J, Nathans J
JournalElife
PubMed ID31066677
Beta-catenin (i.e., canonical Wnt) signaling controls CNS angiogenesis and the blood-brain and blood-retina barriers. To explore the role of the Discs large/membrane-associated guanylate kinase (Dlg/MAGUK) family of scaffolding proteins in beta-catenin signaling, we studied vascular endothelial cell (EC)-specific knockout of Dlg1/SAP97. EC-specific loss of Dlg1 produces a retinal vascular phenotype ... More
Cytoskeletal Control of Antigen-Dependent T Cell Activation.
AuthorsColin-York H, Javanmardi Y, Skamrahl M, Kumari S, Chang VT, Khuon S, Taylor A, Chew TL, Betzig E, Moeendarbary E, Cerundolo V, Eggeling C, Fritzsche M
JournalCell Rep
PubMed ID30893608
Cytoskeletal actin dynamics is essential for T cell activation. Here, we show evidence that the binding kinetics of the antigen engaging the T cell receptor influences the nanoscale actin organization and mechanics of the immune synapse. Using an engineered T cell system expressing a specific T cell receptor and stimulated by a range of ... More
Distinct Roles for Rac1 in Sertoli Cell Function during Testicular Development and Spermatogenesis.
AuthorsHeinrich A, Potter SJ, Guo L, Ratner N, DeFalco T
JournalCell Rep
PubMed ID32294451
Sertoli cells are supporting cells of the testicular seminiferous tubules, which provide a nurturing environment for spermatogenesis. Adult Sertoli cells are polarized so that they can simultaneously support earlier-stage spermatogenic cells (e.g., spermatogonia) basally and later-stage cells (e.g., spermatids) apically. To test the consequences of disrupting cell polarity in Sertoli ... More
Novel Human Polymorphisms Define a Key Role for the SLC26A6-STAS Domain in Protection From Ca
AuthorsShimshilashvili L, Aharon S, Moe OW, Ohana E
JournalFront Pharmacol
PubMed ID32317970
Impaired homeostasis of the carboxylic acids oxalate and citrate, dramatically increases the risk for the formation of Ca
GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export of E-cadherin, MMP14, and CFTR ?F508.
AuthorsLucken-Ardjomande Häsler S, Vallis Y, Pasche M, McMahon HT
JournalJ Cell Biol
PubMed ID32344433
In addition to the classical pathway of secretion, some transmembrane proteins reach the plasma membrane through alternative routes. Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner. GRAFs are membrane-binding proteins associated with tubules and vesicles. We found extensive colocalization of GRAF1b/2 with Rab8a/b ... More
Development of a therapeutic anti-HtrA1 antibody and the identification of DKK3 as a pharmacodynamic biomarker in geographic atrophy.
AuthorsTom I, Pham VC, Katschke KJ, Li W, Liang WC, Gutierrez J, Ah Young A, Figueroa I, Eshghi ST, Lee CV, Kanodia J, Snipas SJ, Salvesen GS, Lai P, Honigberg L, van Lookeren Campagne M, Kirchhofer D, Baruch A, Lill JR
JournalProc Natl Acad Sci U S A
PubMed ID32345717
Genetic polymorphisms in the region of the trimeric serine hydrolase high-temperature requirement 1 (