Chemical cross-linking provides a model of the gamma-secretase complex subunit architecture and evidence for close proximity of the C-terminal fragment of presenilin with APH-1.
AuthorsSteiner H, Winkler E, Haass C
JournalJ Biol Chem
PubMed ID18801744
'Gamma-secretase is an intramembrane cleaving aspartyl protease complex intimately implicated in Alzheimer disease pathogenesis. The protease is composed of the catalytic subunit presenilin (PS1 or PS2), the substrate receptor nicastrin (NCT), and two additional subunits, APH-1 (APH-1a, as long and short splice forms (APH-1aL, APH-1aS), or APH-1b) and PEN-2. Apart ... More
The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse.
AuthorsLarimore J, Tornieri K, Ryder PV, Gokhale A, Zlatic SA, Craige B, Lee JD, Talbot K, Pare JF, Smith Y, Faundez V
JournalMol Biol Cell
PubMed ID21998198
'Dysbindin assembles into the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which interacts with the adaptor protein complex 3 (AP-3), mediating a common endosome-trafficking route. Deficiencies in AP-3 and BLOC-1 affect synaptic vesicle composition. However, whether AP-3-BLOC-1-dependent sorting events that control synapse membrane protein content take place in cell bodies ... More
Molecular dissection of Erv26p identifies separable cargo binding and coat protein sorting activities.
AuthorsBue CA, Barlowe C
JournalJ Biol Chem
PubMed ID19574229
'Efficient export of secretory alkaline phosphatase (ALP) from the endoplasmic reticulum depends on the conserved transmembrane sorting adaptor Erv26p/Svp26p. In the present study we investigated the mechanism by which Erv26p couples pro-ALP to the coat protein complex II (COPII) export machinery. Site-specific mutations were introduced into Erv26p, and mutant proteins ... More
Compartmentalized cyclic adenosine 3',5'-monophosphate at the plasma membrane clusters PDE3A and cystic fibrosis transmembrane conductance regulator into microdomains.
AuthorsPenmatsa H, Zhang W, Yarlagadda S, Li C, Conoley VG, Yue J, Bahouth SW, Buddington RK, Zhang G, Nelson DJ, Sonecha MD, Manganiello V, Wine JJ, Naren AP
JournalMol Biol Cell
PubMed ID20089840
Formation of multiple-protein macromolecular complexes at specialized subcellular microdomains increases the specificity and efficiency of signaling in cells. In this study, we demonstrate that phosphodiesterase type 3A (PDE3A) physically and functionally interacts with cystic fibrosis transmembrane conductance regulator (CFTR) channel. PDE3A inhibition generates compartmentalized cyclic adenosine 3',5'-monophosphate (cAMP), which further ... More
Association of Rho-associated protein kinase 1 with E-cadherin complexes is mediated by p120-catenin.
AuthorsSmith AL, Dohn MR, Brown MV, Reynolds AB
JournalMol Biol Cell
PubMed ID22031287
The dynamic functional linkage of cadherins with the underlying actin cytoskeleton is tightly regulated to achieve proper cell-cell adhesion. p120-catenin (p120) regulates both cadherin stability and actin dynamics, but the relationship between these two functions remains unclear. Using a novel proteomic approach called reversible cross-link immunoprecipitation, or ReCLIP, we previously ... More
Clathrin-dependent mechanisms modulate the subcellular distribution of class C Vps/HOPS tether subunits in polarized and nonpolarized cells.
AuthorsZlatic SA, Tornieri K, L'Hernault SW, Faundez V
JournalMol Biol Cell
PubMed ID21411634
Coats define the composition of carriers budding from organelles. In addition, coats interact with membrane tethers required for vesicular fusion. The yeast AP-3 (Adaptor Protein Complex 3) coat and the class C Vps/HOPS (HOmotypic fusion and Protein Sorting) tether follow this model as their interaction occurs at the carrier fusion ... More
Identification of a thyroid hormone response element in the mouse Kruppel-like factor 9 gene to explain its postnatal expression in the brain.
AuthorsDenver RJ, Williamson KE
JournalEndocrinology
PubMed ID19359381
Brain development is critically dependent on thyroid hormone (T(3)). Krüppel-like factor 9 (Klf9) is a T(3)-inducible gene in developing rat brain, and several lines of evidence support that KLF9 plays a key role in neuronal morphogenesis. Here we extend our findings to the mouse and demonstrate the presence of a ... More
Wild-type opaque2 and defective opaque2 polypeptides form complexes in maize endosperm cells and bind the opaque2-zein target site.
AuthorsGavazzi F, Lazzari B, Ciceri P, Gianazza E, Viotti A
JournalPlant Physiol
PubMed ID17827273
The Opaque2 (O2) basic leucine (Leu)-zipper transcriptional activator controls the expression of several genes in maize (Zea mays). We investigated the phosphorylation extent of wild-type O2 and mutant-defective or mutant-truncated o2 polypeptides in endosperm cells, their subcellular localization, participation in complex formation, and involvement in functional activity. Besides wild type, ... More