Abstract:
:Clathrin-mediated endocytosis regulates the internalization of many nutrient and signaling receptors. Clathrin and endocytic accessory proteins are recruited to receptors by specific adaptors. The adaptor Disabled-2 (Dab2) recruits its cargoes, including the low-density lipoprotein receptor (LDLR), and mediates endocytosis, even when the major adaptor protein AP2 is depleted. We hypothesized that the accessory proteins normally recruited by AP2 may be recruited by Dab2 if AP2 is absent. We identified one such accessory protein, the F-BAR protein FCH domain only-2 (FCHO2), as a major Dab2-interacting protein. The μ-homology domain (μHD) of FCHO2 binds directly to DPF sequences in Dab2 that also bind AP2. Disrupting the Dab2-FCHO2 interaction inhibited Dab2-mediated LDLR endocytosis in AP2-depleted cells. Depleting FCHO2 reduced the number but increased the size of clathrin structures on the adherent surface of HeLa cells and inhibited LDLR and transferrin receptor clustering. However, LDLR was internalized efficiently by FCHO2-deficient cells when additional time was provided for LDLR to enter the enlarged structures before budding, suggesting that later steps of endocytosis are normal under these conditions. These results indicate FCHO2 regulates the size of clathrin structures, and its interaction with Dab2 is needed for LDLR endocytosis under conditions of low AP2.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Mulkearns EE,Cooper JAdoi
10.1091/mbc.E11-09-0812subject
Has Abstractpub_date
2012-04-01 00:00:00pages
1330-42issue
7eissn
1059-1524issn
1939-4586pii
mbc.E11-09-0812journal_volume
23pub_type
杂志文章abstract::To determine how the human cdc25 gene product acts to regulate p34cdc2 at the G2 to M transition, we have overproduced the full-length protein (cdc25Hs) as well as several deletion mutants in bacteria as glutathione-S-transferase fusion proteins. The wild-type cdc25Hs gene product was synthesized as an 80-kDa fusion p...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.3.1.73
更新日期:1992-01-01 00:00:00
abstract::Subcellular targeting and the activity of facilitative glucose transporters are likely to be regulated by interactions with cellular proteins. This report describes the identification and characterization of a protein, GLUT1 C-terminal binding protein (GLUT1CBP), that binds via a PDZ domain to the C terminus of GLUT1....
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.10.4.819
更新日期:1999-04-01 00:00:00
abstract::The PDZ domain-containing protein CAL mediates lysosomal trafficking and degradation of CFTR. Here we demonstrate the involvement of a CAL-binding SNARE protein syntaxin 6 (STX6) in this process. Overexpression of STX6, which colocalizes and coimmunoprecipitates with CAL, dramatically reduces the steady-state level an...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-03-0229
更新日期:2010-04-01 00:00:00
abstract::Synaptic vesicles (SV) are generated by two different mechanisms, one AP-2 dependent and one AP-3 dependent. It has been uncertain, however, whether these mechanisms generate SV that differ in molecular composition. We explored this hypothesis by analyzing the targeting of ZnT3 and synaptophysin both to PC12 synaptic-...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-06-0401
更新日期:2004-02-01 00:00:00
abstract::Integrin alpha 3A cytoplasmic tail phosphorylation was mapped to amino acid S1042, as determined by mass spectrometry, and confirmed by mutagenesis. This residue occurs within a "QPSXXE" motif conserved in multiple alpha chains (alpha 3A, alpha 6A, alpha 7A), from multiple species. Phosphorylation of alpha 3A and alph...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.12.2.351
更新日期:2001-02-01 00:00:00
abstract::The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids. To perform these functions, the Golgi forms a multilayer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners. Depletion of GRASP proteins disru...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E18-07-0462
更新日期:2019-03-15 00:00:00
abstract::DEAD box proteins are putative RNA helicases that function in all aspects of RNA metabolism, including translation, ribosome biogenesis, and pre-mRNA splicing. Because many processes involving RNA metabolism are spatially organized within the cell, we examined the subcellular distribution of a human DEAD box protein, ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.12.10.3046
更新日期:2001-10-01 00:00:00
abstract::Formins have conserved roles in cell polarity and cytokinesis and directly nucleate actin filament assembly through their FH2 domain. Here, we define the active region of the yeast formin Bni1 FH2 domain and show that it dimerizes. Mutations that disrupt dimerization abolish actin assembly activity, suggesting that di...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-08-0621
更新日期:2004-02-01 00:00:00
abstract::The receptor-tyrosine kinase (RTK)/Ras/Raf pathway is an essential cascade for mediating growth factor signaling. It is abnormally overactive in almost all human cancers. The downstream targets of the pathway are members of the extracellular regulated kinases (Erk1/2) family, suggesting that this family is a mediator ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-07-0521
更新日期:2016-03-15 00:00:00
abstract::The assembly of metazoan Sm-class small nuclear ribonucleoproteins (snRNPs) is an elaborate, step-wise process that takes place in multiple subcellular compartments. The initial steps, including formation of the core RNP, are mediated by the survival motor neuron (SMN) protein complex. Loss-of-function mutations in hu...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-01-0024
更新日期:2009-01-01 00:00:00
abstract::Osteosarcoma is the most frequent primary tumor of bone and is characterized by its high tendency to metastasize in lungs. Although treatment in cases of early diagnosis results in a 5-yr survival rate of nearly 60%, the prognosis for patients with secondary lesions at diagnosis is poor, and their 5-yr survival rate r...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E18-08-0545
更新日期:2019-03-21 00:00:00
abstract::We report the identification of Cdc7/Dbf4 phosphorylation sites in human MCM2 and the determination of the role of Cdc7/Dbf4 phosphorylation of MCM2 in the initiation of DNA replication. Using immunoblotting, immunofluorescence, and high-speed automated cell-imaging analyses with antibodies specific against MCM2 and C...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e06-03-0241
更新日期:2006-10-01 00:00:00
abstract::The formation and maintenance of the bipolar mitotic spindle apparatus require a complex and balanced interplay of several mechanisms, including the stabilization and separation of polar microtubules and the action of various microtubule motors. Nonmicrotubule elements are also present throughout the spindle apparatus...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.3.11.1259
更新日期:1992-11-01 00:00:00
abstract::Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein expressed on microglia within the brain. Several rare mutations in TREM2 cause an early-onset form of neurodegeneration when inherited homozygously. Here we investigate how these mutations affect the intracellular transport of TREM2. W...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E17-06-0423
更新日期:2017-10-01 00:00:00
abstract::The role of platelet endothelial cell adhesion molecule-1 (PECAM-1) in endothelial cell-cell interactions and its contribution to cadherin-mediated cell adhesion are poorly understood. Such studies have been difficult because all known endothelial cells express PECAM-1. We have used Madin-Darby canine kidney (MDCK) ce...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.8.2793
更新日期:2000-08-01 00:00:00
abstract::In addition to their well-known role in microtubule organization, centrosomes function as signaling platforms and regulate cell cycle events. An important example of such a function is the spindle position checkpoint (SPOC) of budding yeast. SPOC is a surveillance mechanism that ensures alignment of the mitotic spindl...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E14-04-0890
更新日期:2014-07-15 00:00:00
abstract::Integrins are major receptors used by cells to interact with extracellular matrices. In this paper, we identify the first ligands for the beta 8 family of integrins, presenting evidence that integrin heterodimers containing the beta 8 subunit mediate interactions of chick sensory neurons with laminin-1, collagen IV, a...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.6.4.419
更新日期:1995-04-01 00:00:00
abstract::The TOM (translocase of the outer mitochondrial membrane) complex of the outer mitochondrial membrane is required for the import of proteins into the organelle. The core TOM complex contains five proteins, including three small components Tom7, Tom6, and Tom5. We have created single and double mutants of all combinati...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e05-03-0187
更新日期:2005-09-01 00:00:00
abstract::The endoplasmic reticulum (ER) of animal cells is a single, dynamic, and continuous membrane network of interconnected cisternae and tubules spread out throughout the cytosol in direct contact with the nuclear envelope. During mitosis, the nuclear envelope undergoes a major rearrangement, as it rapidly partitions its ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-04-0327
更新日期:2009-08-01 00:00:00
abstract::Cell morphogenesis is a complex process that relies on a diverse array of proteins and pathways. We have identified a transglutaminase-like protein (Cyk3p) that functions in fission yeast morphogenesis. The phenotype of a cyk3 knockout strain indicates a primary role for Cyk3p in cytokinesis. Correspondingly, Cyk3p lo...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-07-0656
更新日期:2012-07-01 00:00:00
abstract::The cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase type I (cGKI) pathway regulates many cellular functions. The current study shows that 8-Br-cGMP stimulates the number of attached primary but not that of subcultured murine vascular smooth muscle cells (VSMCs). These effects of 8-Br-cGMP require t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-04-0370
更新日期:2008-10-01 00:00:00
abstract::The inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular calcium channel involved in coupling cell membrane receptors to calcium signal transduction pathways within cells including endocrine cells. Several isoforms (I, II, and III) of IP3Rs have been identified, which are encoded by separate genes, and are...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.7.6.949
更新日期:1996-06-01 00:00:00
abstract::Retroviral assembly is driven by Gag, and nascent viral particles escape cells by recruiting the machinery that forms intralumenal vesicles of multivesicular bodies. In this study, we show that the clathrin adaptor complex AP-1 is involved in retroviral release. The absence of AP-1mu obtained by genetic knock-out or b...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e06-12-1147
更新日期:2007-08-01 00:00:00
abstract::We identified a novel interaction between myosin VI and the GLUT1 transporter binding protein GLUT1CBP(GIPC1) and first proposed that as an adapter molecule it might function to couple vesicle-bound proteins to myosin VI movement. This study refines the model by identifying two myosin VI binding domains in the GIPC1 C...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e04-11-0978
更新日期:2005-09-01 00:00:00
abstract::The homotypic fusion of yeast vacuoles requires the Rab-family GTPase Ypt7p and its effector complex, homotypic fusion and vacuole protein sorting complex (HOPS). Although the vacuolar kinase Yck3p is required for the sensitivity of vacuole fusion to proteins that regulate the Rab GTPase cycle-Gdi1p (GDP-dissociation ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E12-04-0279
更新日期:2012-09-01 00:00:00
abstract::The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio a...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-07-0614
更新日期:2010-07-01 00:00:00
abstract::Dynamic microtubule ends exert pulling and pushing forces on intracellular membranes and organelles. However, the mechanical linkage of microtubule tips to their cargoes is poorly understood. CENP-F is a nonmotor microtubule-binding protein that participates in microtubule binding at kinetochores and in the mitotic re...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-11-0756
更新日期:2017-09-01 00:00:00
abstract::Cortical granules are specialized organelles whose contents interact with the extracellular matrix of the fertilized egg to form the block to polyspermy. In sea urchins, the granule contents form a fertilization envelope (FE), and this construction is critically dependent upon protease activity. An autocatalytic serin...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-11-0843
更新日期:2004-05-01 00:00:00
abstract::Polarized assembly of actin filaments forms the basis of actin-based motility and is regulated both spatially and temporally. Cells use a variety of mechanisms by which intrinsically slower processes are accelerated, and faster ones decelerated, to match rates observed in vivo. Here we discuss how kinetic studies of i...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-06-0352
更新日期:2016-01-01 00:00:00
abstract::Prostaglandins (PGs)--lipid signals produced downstream of cyclooxygenase (COX) enzymes--regulate actin dynamics in cell culture and platelets, but their roles during development are largely unknown. Here we define a new role for Pxt, the Drosophila COX-like enzyme, in regulating the actin cytoskeleton--temporal restr...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E13-07-0366
更新日期:2014-02-01 00:00:00