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
Drug Repurposing as an Antitumor Agent: Disulfiram-Mediated Carbonic Anhydrase 12 and Anion Exchanger 2 Modulation to Inhibit Cancer Cell Migration.
AuthorsHwang S, Shin DM, Hong JH
JournalMolecules
PubMed ID31546841
Disulfiram has been used in the treatment of alcoholism and exhibits an anti-tumor effect. However, the intracellular mechanism of anti-tumor activity of Disulfiram remains unclear. In this study, we focused on the modulatory role of Disulfiram via oncogenic factor carbonic anhydrase CA12 and its associated transporter anion exchanger AE2 in ... More
PSD-95 binding dynamically regulates NLGN1 trafficking and function.
AuthorsJeong J, Pandey S, Li Y, Badger JD, Lu W, Roche KW
JournalProc Natl Acad Sci U S A
PubMed ID31138690
PSD-95 is a scaffolding protein that regulates the synaptic localization of many receptors, channels, and signaling proteins. The NLGN gene family encodes single-pass transmembrane postsynaptic cell adhesion molecules that are important for synapse assembly and function. At excitatory synapses, NLGN1 mediates transsynaptic binding with neurexin, a presynaptic cell adhesion molecule, ... More
Tweety-homolog (
AuthorsHan YE, Kwon J, Won J, An H, Jang MW, Woo J, Lee JS, Park MG, Yoon BE, Lee SE, Hwang EM, Jung JY, Park H, Oh SJ, Lee CJ
JournalExp Neurobiol
PubMed ID31138989
In the brain, a reduction in extracellular osmolality causes water-influx and swelling, which subsequently triggers Cl
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
JournalBiochim Biophys Acta Mol Cell Res
PubMed ID30445147
A plasma membrane amino acid transporter B
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
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
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
Butyrophilin-2A1 Directly Binds Germline-Encoded Regions of the V?9Vd2 TCR and Is Essential for Phosphoantigen Sensing.
AuthorsKarunakaran MM, Willcox CR, Salim M, Paletta D, Fichtner AS, Noll A, Starick L, Nöhren A, Begley CR, Berwick KA, Chaleil RAG, Pitard V, Déchanet-Merville J, Bates PA, Kimmel B, Knowles TJ, Kunzmann V, Walter L, Jeeves M, Mohammed F, Willcox BE, Herrmann T
JournalImmunity
PubMed ID32155411
V?9Vd2 T cells respond in a TCR-dependent fashion to both microbial and host-derived pyrophosphate compounds (phosphoantigens, or P-Ag). Butyrophilin-3A1 (BTN3A1), a protein structurally related to the B7 family of costimulatory molecules, is necessary but insufficient for this process. We performed radiation hybrid screens to uncover direct TCR ligands and cofactors that potentiate ... More