Defective transport of the obesity mutant PC1/3 N222D contributes to loss of function.

Mutations in the PCSK1 gene encoding prohormone convertase 1/3 (PC1/3) are strongly associated with obesity in humans. The PC1/3(N222D) mutant mouse thus far represents the only mouse model that mimics the PC1/3 obesity phenotype in humans. The present investigation addresses the cell biology of the N222D mutation.

Adaptor protein 2-mediated endocytosis of the β-secretase BACE1 is dispensable for amyloid precursor protein processing.

The β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease that catalyzes the proteolytic processing of APP and other plasma membrane protein precursors. BACE1 cycles between the trans-Golgi network (TGN), the plasma membrane, and endosomes by virtue of signals contained within its cytosolic C-terminal domain. One of these signals is the DXXLL-motif sequence DISLL, which controls transport between the TGN and endosomes via interaction with GGA proteins.

Conservation and diversification of dileucine signal recognition by adaptor protein (AP) complex variants.

The clathrin-associated, heterotetrameric adaptor protein (AP) complexes, AP-1, AP-2, and AP-3, recognize signals in the cytosolic domains of transmembrane proteins, leading to their sorting to endosomes, lysosomes, lysosome-related organelles, and/or the basolateral membrane of polarized epithelial cells. One type of signal, referred to as "dileucine-based," fits the consensus motif (D/E)XXXL(L/I). Previous biochemical analyses showed that (D/E)XXXL(L/I) signals bind to a combination of two subunits of each AP complex, namely the AP-1 γ-σ1, AP-2 α-σ2, and AP-3 δ-σ3 hemicomplexes, and structural studies revealed that an imperfect variant of this motif lacking the (D/E) residue binds to a site straddling the interface of α and σ2.

Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex.

Adaptor protein 4 (AP-4) is the most recently discovered and least well-characterized member of the family of heterotetrameric adaptor protein (AP) complexes that mediate sorting of transmembrane cargo in post-Golgi compartments. Herein, we report the interaction of an YKFFE sequence from the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) with the mu4 subunit of AP-4. Biochemical and X-ray crystallographic analyses reveal that the properties of the APP sequence and the location of the binding site on mu4 are distinct from those of other signal-adaptor interactions.

Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7.

The retromer complex mediates retrograde transport of transmembrane cargo from endosomes to the trans-Golgi network (TGN). Mammalian retromer is composed of a sorting nexin (SNX) dimer that binds to phosphatidylinositol 3-phosphate-enriched endosomal membranes and a vacuolar protein sorting (Vps) 26/29/35 trimer that participates in cargo recognition. The mammalian SNX dimer is necessary but not sufficient for recruitment of the Vps26/29/35 trimer to membranes.

A GPCR involved in post aggregation events in Dictyostelium discoideum.

Dictyostelium has 55 genes encoding seven-transmembrane G-protein-coupled receptors (GPCR) that belong to five of the six GPCR families. GrlA is one of the 17 family 3 GPCRs in Dictyostelium all of which resemble GABA(B) receptors from higher eukaryotes. GrlA is a 90-kDa protein present on the plasma membrane and on membranes of the ER.

GrlJ, a Dictyostelium GABAB-like receptor with roles in post-aggregation development.

Background: The G-protein-coupled receptor (GPCR) family represents the largest and most important group of targets for chemotherapeutics. They are extremely versatile receptors that transduce signals as diverse as biogenic amines, purins, odorants, ions and pheromones from the extracellular compartment to the interior via biochemical processes involving GTP-binding proteins. Until recently, the cyclic AMP receptors (cARs) were the only known G protein coupled receptors in Dictyostelium discoideum.

The annexins of Dictyostelium.

Annexins are a highly conserved ubiquitous family of Ca2+- and phospholipid-binding proteins present in nearly all eukaryotic cells. Analysis of the Dictyostelium genome revealed the presence of two annexin genes, the annexin C1 gene (nxnA) giving rise to two isoforms of 47 and 51 kDa (previously synexin), and the annexin C2 gene (nxnB) coding for a 56-kDa protein with 33% sequence identity to annexin C1. Annexin C2 is expressed at very low and constant levels throughout development.

The Dictyostelium repertoire of seven transmembrane domain receptors.

The availability of fully sequenced genomes allows the in silico analysis of whole gene families in a given genome. A particularly large and interesting gene family is the G-protein-coupled receptor family. These receptors detect a variety of extracellular signals and transduce them, generally via heterotrimeric G-proteins, to effector proteins inside the cell and thus elicit a physiological response.

O-phthalic acid, a dead-end product in one of the two pathways of phenanthrene degradation in Pseudomonas sp. strain PP2.

Phenanthrene is degraded via either o-phthalic acid or 1, 2-dihydroxynaphthalene in bacteria. A soil isolate Pseudomonas sp. strain PP2 degrades phenanthrene as the sole source of carbon, but failed to utilize naphthalene [Prabhu and Phale (2003) Appl Microbiol Biotechnol 61:342-351].