Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis.
AuthorsBlanc L, Ciciotte SL, Gwynn B, Hildick-Smith GJ, Pierce EL, Soltis KA, Cooney JD, Paw BH, Peters LL,
JournalProc Natl Acad Sci U S A
PubMed ID22773809
Phenotype-driven approaches to gene discovery using inbred mice have been instrumental in identifying genetic determinants of inherited blood dyscrasias. The recessive mutant scat (severe combined anemia and thrombocytopenia) alternates between crisis and remission episodes, indicating an aberrant regulatory feedback mechanism common to erythrocyte and platelet formation. Here, we identify a ... More
Adaptive changes of duodenal iron transport proteins in celiac disease.
AuthorsBarisani D, Parafioriti A, Bardella MT, Zoller H, Conte D, Armiraglio E, Trovato C, Koch RO, Weiss G,
JournalPhysiol Genomics
PubMed ID15054143
Iron deficiency is a manifestation of celiac disease (CD) usually attributed to a decreased absorptive surface, although no data on the regulation of iron transport under these conditions are currently available. Our aim was to evaluate divalent metal transporter 1 (DMT1), duodenal cytochrome b (Dcytb), ferroportin 1 (FP1), hephaestin, and ... More
Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains.
AuthorsHuang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP, Yona S, Stacey M, Gordon S, Chang GW, Lin HH
JournalMol Cell Biol
PubMed ID22310662
'The adhesion class G protein-coupled receptors (adhesion-GPCRs) play important roles in diverse biological processes ranging from immunoregulation to tissue polarity, angiogenesis, and brain development. These receptors are uniquely modified by self-catalytic cleavage at a highly conserved GPCR proteolysis site (GPS) dissecting the receptor into an extracellular subunit (a) and a ... More
AuthorsAbou-Zeid N, Pandjaitan R, Sengmanivong L, David V, Le Pavec G, Salamero J, Zahraoui A
JournalMol Biol Cell
PubMed ID21795389
'Small GTPase Rabs are required for membrane protein sorting/delivery to precise membrane domains. Rab13 regulates epithelial tight junction assembly and polarized membrane transport. Here we report that Molecule Interacting with CasL (MICAL)-like1 (MICAL-L1) interacts with GTP-Rab13 and shares a similar domain organization with MICAL. MICAL-L1 has a calponin homology (CH), ... More
BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production.
AuthorsFotinopoulou A, Tsachaki M, Vlavaki M, Poulopoulos A, Rostagno A, Frangione B, Ghiso J, Efthimiopoulos S,
JournalJ Biol Chem
PubMed ID16027166
'Transmembrane proteins BRI2 and amyloid precursor protein (APP) co-localize with amyloid beta (Abeta) lesions in sporadic Alzheimer disease and mutations in both precursor proteins are linked to early-onset familial cases of cerebral amyloidosis associated with dementia and/or cerebral hemorrhage. A specific interaction between BRI2 and APP was unveiled by immunoprecipitation ... More
Trafficking of cholera toxin-ganglioside GM1 complex into Golgi and induction of toxicity depend on actin cytoskeleton.
AuthorsBadizadegan K, Wheeler HE, Fujinaga Y, Lencer WI,
JournalAm J Physiol Cell Physiol
PubMed ID15294854
'Intestinal epithelial lipid rafts contain ganglioside GM1 that is the receptor for cholera toxin (CT). The ganglioside binds CT at the plasma membrane (PM) and carries the toxin through the trans-Golgi network (TGN) to the endoplasmic reticulum (ER). In the ER, a portion of the toxin unfolds and translocates to ... More
Expression and distribution of nucleoside transporter proteins in the human syncytiotrophoblast.
AuthorsErrasti-Murugarren E, Díaz P, Godoy V, Riquelme G, Pastor-Anglada M
JournalMol Pharmacol
PubMed ID21825094
'The plasma membrane distribution and related biological activity of nucleoside transporter proteins (NTs) were investigated in human syncytiotrophoblast from term placenta using a variety of approaches, including nucleoside uptake measurements into vesicles from selected plasma membrane domains, NT immunohistochemistry, and subcellular localization (basal, heavy, and light apical membranes as well ... More
Masked selection: a straightforward and flexible approach for the selection of binders against specific epitopes and differentially expressed proteins by phage display.
AuthorsEven-Desrumeaux K, Nevoltris D, Lavaut MN, Alim K, Borg JP, Audebert S, Kerfelec B, Baty D, Chames P,
Journal
PubMed ID24361863
'Phage display is a well-established procedure to isolate binders against a wide variety of antigens that can be performed on purified antigens, but also on intact cells. As selection steps are performed in vitro, it is possible to focus the outcome of the selection on relevant epitopes by performing some ... More
Molecular characterization of a trafficking organelle: dissecting the axonal paths of calsyntenin-1 transport vesicles.
AuthorsSteuble M, Gerrits B, Ludwig A, Mateos JM, Diep TM, Tagaya M, Stephan A, Schätzle P, Kunz B, Streit P, Sonderegger P,
JournalProteomics
PubMed ID20925061
'Kinesin motors play crucial roles in the delivery of membranous cargo to its destination and thus for the establishment and maintenance of cellular polarization. Recently, calsyntenin-1 was identified as a cargo-docking protein for Kinesin-1-mediated axonal transport of tubulovesicular organelles along axons of central nervous system neurons. To further define the ... More
Microanatomy of axon/glial signaling during Wallerian degeneration.
AuthorsGuertin AD, Zhang DP, Mak KS, Alberta JA, Kim HA,
JournalJ Neurosci
PubMed ID15800203
'How do myelinated axons signal to the nuclei of cells that enwrap them? The cell bodies of oligodendrocytes and Schwann cells are segregated from axons by multiple layers of bimolecular lipid leaflet and myelin proteins. Conventional signal transduction strategies would seem inadequate to the challenge without special adaptations. Wallerian degeneration ... More
Loss of the von Hippel Lindau tumor suppressor disrupts iron homeostasis in renal carcinoma cells.
AuthorsAlberghini A, Recalcati S, Tacchini L, Santambrogio P, Campanella A, Cairo G,
JournalJ Biol Chem
PubMed ID15985433
'Given the modulation of iron metabolism by hypoxia and the high iron requirement of neoplastic cells, we investigated iron metabolism in a human renal cancer cell line with a mutated von Hippel Lindau (VHL) tumor suppressor gene (RCC10) and in a transfectant clone with wild-type VHL (RCC63). The loss of ... More
Rab15 mediates an early endocytic event in Chinese hamster ovary cells.
AuthorsZuk PA, Elferink LA
JournalJ Biol Chem
PubMed ID10428799
'Rab GTPases comprise a large family of monomeric proteins that regulate a diverse number of membrane trafficking events, including endocytosis. In this paper, we examine the subcellular distribution and function of the GTPase Rab15. Our biochemical and confocal immunofluorescence studies demonstrate that Rab15 associates with the transferrin receptor, a marker ... More
Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells.
AuthorsYan HH, Mruk DD, Lee WM, Cheng CY,
JournalFASEB J
PubMed ID18192323
During spermatogenesis in the mammalian testis, preleptotene/leptotene spermatocytes differentiate from type B spermatogonia and traverse the blood-testis barrier (BTB) at stage VIII of the seminiferous epithelial cycle for further development. This timely movement of germ cells involves extensive junction restructuring at the BTB. Previous studies have shown that these events ... More
Epidermal growth factor receptors are localized to lipid rafts that contain a balance of inner and outer leaflet lipids: a shotgun lipidomics study.
AuthorsPike LJ, Han X, Gross RW,
JournalJ Biol Chem
PubMed ID15917253
The epidermal growth factor (EGF) receptor partitions into lipid rafts made using a detergent-free method, but is extracted from low density fractions by Triton X-100. By screening several detergents, we identified Brij 98 as a detergent in which the EGF receptor is retained in detergent-resistant membrane fractions. To identify the ... More
The DnaJ-domain protein RME-8 functions in endosomal trafficking.
AuthorsGirard M, Poupon V, Blondeau F, McPherson PS,
JournalJ Biol Chem
PubMed ID16179350
Through a proteomic analysis of clathrin-coated vesicles from rat liver we identified the mammalian homolog of receptor-mediated endocytosis 8 (RME-8), a DnaJ domain-containing protein originally identified in a screen for endocytic defects in Caenorhabditis elegans. Mammalian RME-8 has a broad tissue distribution, and affinity selection assays reveal the ubiquitous chaperone ... More
Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking and long term synaptic depression.
AuthorsSnyder EM, Colledge M, Crozier RA, Chen WS, Scott JD, Bear MF,
JournalJ Biol Chem
PubMed ID15718245
Expression of N-methyl d-aspartate (NMDA) receptor-dependent homosynaptic long term depression at synapses in the hippocampus and neocortex requires the persistent dephosphorylation of postsynaptic protein kinase A substrates. An attractive mechanism for expression of long term depression is the loss of surface AMPA (alpha-amino-3-hydroxy-5-methylisoxazale-4-propionate) receptors at synapses. Here we show that ... More
The GDP-bound form of Arf6 is located at the plasma membrane.
AuthorsMacia E, Luton F, Partisani M, Cherfils J, Chardin P, Franco M,
JournalJ Cell Sci
PubMed ID15126638
The function of Arf6 has been investigated largely by using the T27N and the Q67L mutants, which are thought to be blocked in GDP- and GTP-bound states, respectively. However, these mutants have been poorly characterized biochemically. Here, we found that Arf6(T27N) is not an appropriate marker of the inactive GDP-bound ... More
Multiple regions contribute to membrane targeting of Rab GTPases.
AuthorsAli BR, Wasmeier C, Lamoreux L, Strom M, Seabra MC,
JournalJ Cell Sci
PubMed ID15561774
Small GTPases of the Rab family are key regulators of membrane trafficking. Each Rab shows a characteristic subcellular distribution, and may serve as an important determinant of organelle identity. The molecular mechanisms responsible for targeting Rabs to specific intracellular compartments, however, remain poorly understood. The divergent C-terminal hypervariable region was ... More
Cross-talk between caveolae and glycosylphosphatidylinositol-rich domains.
AuthorsAbrami L, Fivaz M, Kobayashi T, Kinoshita T, Parton RG, van der Goot FG,
JournalJ Biol Chem
PubMed ID11406621
Most mammalian cells have in their plasma membrane at least two types of lipid microdomains, non-invaginated lipid rafts and caveolae. Glycosylphosphatidylinositol (GPI)-anchored proteins constitute a class of proteins that are enriched in rafts but not caveolae at steady state. We have analyzed the effects of abolishing GPI biosynthesis on rafts, ... More
Ubiquilin-1 modulates ?-secretase-mediated e-site cleavage in neuronal cells.
AuthorsViswanathan J, Haapasalo A, Kurkinen KM, Natunen T, Mäkinen P, Bertram L, Soininen H, Tanzi RE, Hiltunen M,
Journal
PubMed ID23663107
Ubiquilin-1 is an Alzheimer's disease-associated protein, which is known to modulate amyloid precursor protein (APP) processing, amyloid-ß (Aß) secretion, and presenilin-1 (PS1) accumulation. Here, we aim to elucidate the molecular mechanisms by which full-length transcript variant 1 of ubiquilin-1 (TV1) affects APP processing and ?-secretase function in human neuroblastoma cells ... More
Cullin-3 regulates late endosome maturation.
AuthorsHuotari J, Meyer-Schaller N, Hubner M, Stauffer S, Katheder N, Horvath P, Mancini R, Helenius A, Peter M
JournalProc Natl Acad Sci U S A
PubMed ID22219362
Cullin-3 (Cul3) functions as a scaffolding protein in the Bric-a-brac, Tramtrack, Broad-complex (BTB)-Cul3-Rbx1 ubiquitin E3 ligase complex. Here, we report a previously undescribed role for Cul3 complexes in late endosome (LE) maturation. RNAi-mediated depletion of Cul3 results in a trafficking defect of two cargoes of the endolysosomal pathway, influenza A ... More
Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function.
AuthorsPerrotta C, Bizzozero L, Cazzato D, Morlacchi S, Assi E, Simbari F, Zhang Y, Gulbins E, Bassi MT, Rosa P, Clementi E
JournalJ Biol Chem
PubMed ID20956541
Acid sphingomyelinase (A-SMase) is an important enzyme in sphingolipid metabolism and plays key roles in apoptosis, immunity, development, and cancer. In addition, it mediates cytotoxicity of cisplatin and some other chemotherapeutic drugs. The mechanism of A-SMase activation is still undefined. We now demonstrate that, upon CD95 stimulation, A-SMase is activated ... More
Transmembrane domain determinants of CD4 Downregulation by HIV-1 Vpu.
AuthorsMagadán JG, Bonifacino JS
JournalJ Virol
PubMed ID22090097
The transmembrane domains (TMDs) of integral membrane proteins do not merely function as membrane anchors but play active roles in many important biological processes. The downregulation of the CD4 coreceptor by the Vpu protein of HIV-1 is a prime example of a process that is dependent on specific properties of ... More
Endocytosis resumes during late mitosis and is required for cytokinesis.
AuthorsSchweitzer JK, Burke EE, Goodson HV, D'Souza-Schorey C
JournalJ Biol Chem
PubMed ID16207714
Recent work has underscored the importance of membrane trafficking events during cytokinesis. For example, targeted membrane secretion occurs at the cleavage furrow in animal cells, and proteins that regulate endocytosis also influence the process of cytokinesis. Nonetheless, the prevailing dogma is that endosomal membrane trafficking ceases during mitosis and resumes ... More
Lipid raft endocytosis and exosomal transport facilitate extracellular trafficking of annexin A2.
AuthorsValapala M, Vishwanatha JK
JournalJ Biol Chem
PubMed ID21737841
Annexin A2 (AnxA2), a Ca(2+)-dependent phospholipid-binding protein, is known to associate with the plasma membrane and the endosomal system. Within the plasma membrane, AnxA2 associates in a Ca(2+) dependent manner with cholesterol-rich lipid raft microdomains. Here, we show that the association of AnxA2 with the lipid rafts is influenced not ... More
Functional ESCRT machinery is required for constitutive recycling of claudin-1 and maintenance of polarity in vertebrate epithelial cells.
AuthorsDukes JD, Fish L, Richardson JD, Blaikley E, Burns S, Caunt CJ, Chalmers AD, Whitley P
JournalMol Biol Cell
PubMed ID21757541
Genetic screens in Drosophila have identified regulators of endocytic trafficking as neoplastic tumor suppressor genes. For example, Drosophila endosomal sorting complex required for transport (ESCRT) mutants lose epithelial polarity and show increased cell proliferation, suggesting that ESCRT proteins could function as tumor suppressors. In this study, we show for the ... More