AuthorsCreighton J, Jian M, Sayner S, Alexeyev M, Insel PA,
JournalFASEB J
PubMed ID21680893
'The vascular endothelium responds to damage through activation of multiple signaling events that restore cell-cell adhesion and vascular integrity. However, the molecular mechanisms that integrate these events are not clearly defined. Herein, we identify a previously unexpected role for adenosine monophosphate-activated protein kinase (AMPK) in pulmonary microvascular endothelial cell (PMVEC) ... More
Restriction of receptor movement alters cellular response: physical force sensing by EphA2.
AuthorsSalaita K, Nair PM, Petit RS, Neve RM, Das D, Gray JW, Groves JT,
JournalScience
PubMed ID20223987
'Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, ... More
Dynamics of flagellum- and pilus-mediated association of Pseudomonas aeruginosa with contact lens surfaces.
AuthorsTran VB, Fleiszig SM, Evans DJ, Radke CJ,
JournalAppl Environ Microbiol
PubMed ID21498762
'Flagella and pili are appendages that modulate attachment of Pseudomonas aeruginosa to solid surfaces. However, previous studies have mostly reported absolute attachment. Neither the dynamic roles of these appendages in surface association nor those of attachment phenotypes have been quantified. We used video microscopy to address this issue. Unworn, sterile, ... More
The histone deacetylase Hos2 forms an Hsp42-dependent cytoplasmic granule in quiescent yeast cells.
AuthorsLiu IC, Chiu SW, Lee HY, Leu JY,
JournalMol Biol Cell
PubMed ID22337769
'One of many physiological adjustments in quiescent cells is spatial regulation of specific proteins and RNA important for the entry to or exit from the stationary phase. By examining the localization of epigenetic-related proteins in Saccharomyces cerevisiae, we observed the formation of a reversible cytosolic ' ... More
Transmembrane water-flux through SLC4A11: a route defective in genetic corneal diseases.
AuthorsVilas GL, Loganathan SK, Liu J, Riau AK, Young JD, Mehta JS, Vithana EN, Casey JR,
Journal
PubMed ID23813972
'Three genetic corneal dystrophies [congenital hereditary endothelial dystrophy type 2 (CHED2), Harboyan syndrome and Fuchs endothelial corneal dystrophy] arise from mutations of the SLC4a11 gene, which cause blindness from fluid accumulation in the corneal stroma. Selective transmembrane water conductance controls cell size, renal fluid reabsorption and cell division. All known ... More
Rab8a regulates the exocyst-mediated kiss-and-run discharge of the Dictyostelium contractile vacuole.
AuthorsEssid M, Gopaldass N, Yoshida K, Merrifield C, Soldati T,
JournalMol Biol Cell
PubMed ID22323285
'Water expulsion by the contractile vacuole (CV) in Dictyostelium is carried out by a giant kiss-and-run focal exocytic event during which the two membranes are only transiently connected but do not completely merge. We present a molecular dissection of the GTPase Rab8a and the exocyst complex in tethering of the ... More
Conformational Transitions of the Cross-linking Domains of Elastin during Self-assembly.
Elastin is the intrinsically disordered polymeric protein imparting the exceptional properties of extension and elastic recoil to the extracellular matrix of most vertebrates. The monomeric precursor of elastin, tropoelastin, as well as polypeptides containing smaller subsets of the tropoelastin sequence, can self-assemble through a colloidal phase separation process called coacervation. ... More
Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis.
AuthorsMaekawa M, Terasaka S, Mochizuki Y, Kawai K, Ikeda Y, Araki N, Skolnik EY, Taguchi T, Arai H,
Journal
PubMed ID24591580
Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and solutes are internalized into cells. Macropinocytosis starts with the formation of membrane ruffles at the plasma membrane and ends with their closure. The transient and sequential emergence of phosphoinositides PI(3,4,5)P3 and PI(3,4)P2 in the membrane ruffles is essential ... More
Tracking individual membrane proteins using quantum dots.
AuthorsCourty S, Dahan M,
Journal
PubMed ID24086060
Single-particle tracking of individual membrane molecules is now the method of choice to decipher the molecular organization of the plasma membrane. By labeling proteins or lipids with latex beads, 40-nm gold nanoparticles, or small organic fluorophores, it is possible to analyze the mechanisms controlling their lateral dynamics. Semiconductor quantum dots ... More
How vinculin regulates force transmission.
AuthorsDumbauld DW, Lee TT, Singh A, Scrimgeour J, Gersbach CA, Zamir EA, Fu J, Chen CS, Curtis JE, Craig SW, García AJ,
Journal
PubMed ID23716647
Focal adhesions mediate force transfer between ECM-integrin complexes and the cytoskeleton. Although vinculin has been implicated in force transmission, few direct measurements have been made, and there is little mechanistic insight. Using vinculin-null cells expressing vinculin mutants, we demonstrate that vinculin is not required for transmission of adhesive and traction ... More
Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility.
AuthorsFriesland A, Zhao Y, Chen YH, Wang L, Zhou H, Lu Q,
JournalProc Natl Acad Sci U S A
PubMed ID23284167
Signaling through the Rho family of small GTPases has been intensely investigated for its crucial roles in a wide variety of human diseases. Although RhoA and Rac1 signaling pathways are frequently exploited with the aid of effective small molecule modulators, studies of the Cdc42 subclass have lagged because of a ... More
Leucine stimulates insulin secretion via down-regulation of surface expression of adrenergic a2A receptor through the mTOR (mammalian target of rapamycin) pathway: implication in new-onset diabetes in renal transplantation.
AuthorsYang J, Dolinger M, Ritaccio G, Mazurkiewicz J, Conti D, Zhu X, Huang Y,
JournalJ Biol Chem
PubMed ID22645144
The amino acid leucine is a potent secretagogue, capable of inducing insulin secretion. It also plays an important role in the regulation of mTOR activity, therefore, providing impetus to investigate if a leucine-sensing mechanism in the mTOR pathway is involved in insulin secretion. We found that leucine-induced insulin secretion was ... More
Basic residues in the T-cell receptor ? cytoplasmic domain mediate membrane association and modulate signaling.
AuthorsZhang H, Cordoba SP, Dushek O, van der Merwe PA,
JournalProc Natl Acad Sci U S A
PubMed ID22084078
The T-cell receptor (TCR) consists of a TCRaß heterodimer, a TCR? homodimer, and CD3?e and CD3de heterodimers. The precise mechanism of T-cell triggering following TCR ligand engagement remains elusive. Previous studies reported that the cytoplasmic tail of CD3e binds to the plasma membrane through a basic residue-rich stretch (BRS) and ... More
Purification of pseudopodia from polarized cells reveals redistribution and activation of Rac through assembly of a CAS/Crk scaffold.
AuthorsCho SY, Klemke RL
JournalJ Cell Biol
PubMed ID11839772
Initiation of cell migration requires morphological polarization with formation of a dominant leading pseudopodium and rear compartment. A molecular understanding of this process has been limited, due to the inability to biochemically separate the leading pseudopodium from the rear of the cell. Here we examine the spatio-temporal localization and activation ... More
Imaging kinase--AKAP79--phosphatase scaffold complexes at the plasma membrane in living cells using FRET microscopy.
AuthorsOliveria SF, Gomez LL, Dell'Acqua ML
JournalJ Cell Biol
PubMed ID12507994
Scaffold, anchoring, and adaptor proteins coordinate the assembly and localization of signaling complexes providing efficiency and specificity in signal transduction. The PKA, PKC, and protein phosphatase-2B/calcineurin (CaN) scaffold protein A-kinase anchoring protein (AKAP) 79 is localized to excitatory neuronal synapses where it is recruited to glutamate receptors by interactions with ... More
Calcium-mediated transductive systems and functionally active gap junctions in astrocyte-like GL15 cells.
AuthorsMariggio MA, Mazzoleni G, Pietrangelo T, Guarnieri S, Morabito C, Steimberg N, Fano G
JournalBMC Physiol
PubMed ID11384510
BACKGROUND: It has been proposed that GL15, a human cell line derived from glioblastoma multiforme, is a possible astroglial-like cell model, based on the presence of cytoplasmic glial fibrillary acidic protein. RESULTS: The aim of this work was to delineate the functional characteristics of GL15 cells using various experimental approaches, ... More