Abstract:
:UNC-104 (KIF1A) is a kinesin motor that transports synaptic vesicles from the neuronal cell body to the terminal. Previous in vitro studies have shown that a Dictyostelium relative of UNC-104 transports liposomes containing acidic phospholipids, but whether this interaction is needed for the recognition and transport of synaptic vesicles in metazoans remains unexplored. Here, we have introduced mutations in the nonmotor domain of UNC-104 and examined whether these mutant motors can rescue an unc-104 Caenorhabditis elegans strain. We show that a pleckstrin homology (PH) domain in UNC-104 is essential for membrane transport in living C. elegans, that this PH domain binds specifically to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)), and that point mutants in the PH domain that interfere with PI(4,5)P(2) binding in vitro also interfere with UNC-104 function in vivo. Several other lipid-binding modules could not effectively substitute for the UNC-104 PH domain in this in vivo assay. Real time imaging also revealed that a lipid-binding point mutation in the PH domain reduced movement velocity and processivity of individual UNC-104::GFP punctae in neurites. These results reveal a critical role for PI(4,5)P(2) binding in UNC-104-mediated axonal transport and shows that the cargo-binding properties of the distal PH domain can affect motor output.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Klopfenstein DR,Vale RDdoi
10.1091/mbc.e04-04-0326keywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
3729-39issue
8eissn
1059-1524issn
1939-4586pii
E04-04-0326journal_volume
15pub_type
杂志文章abstract::Cell migration is involved in various physiological and pathogenic events, and the complex underlying molecular mechanisms have not been fully elucidated. The simple eukaryote Dictyostelium discoideum displays chemotactic locomotion in stages of its life cycle. By characterizing a Dictyostelium mutant defective in che...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E14-05-0972
更新日期:2015-03-15 00:00:00
abstract::A primary cilium is found on most mammalian cells, where it acts as a cellular antenna for the reception of both mechanical and chemical signals. A variety of diseases are associated with defective ciliogenesis, reflecting the ubiquity of the function of cilia and the number of proteins required for their assembly. Pr...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E18-02-0088
更新日期:2018-07-01 00:00:00
abstract::The eukaryotic flagellum is a large structure into which specific constituent proteins must be targeted, transported and assembled after their synthesis in the cytoplasm. Using Trypanosoma brucei and a proteomic approach, we have identified and characterized a novel set of adenylate kinase proteins that are localized ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e04-03-0217
更新日期:2004-07-01 00:00:00
abstract::A cell surface proteoglycan, syndecan-1, has been shown to participate in the maintenance of the epithelial cell morphology. A point mutated activated c-Ha-ras gene under the control of the glucocorticoid inducible MMTV-LTR promoter was transfected into the mouse mammary epithelial cell line, NOG-8. The NOG-8 ras cell...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.4.8.849
更新日期:1993-08-01 00:00:00
abstract::Tolerance to desiccation in cultures of Saccharomyces cerevisiae is inducible; only one in a million cells from an exponential culture survive desiccation compared with one in five cells in stationary phase. Here we exploit the desiccation sensitivity of exponentially dividing cells to understand the stresses imposed ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E12-07-0524
更新日期:2013-01-01 00:00:00
abstract::ORP1L is a member of the human oxysterol-binding protein (OSBP) family. ORP1L localizes to late endosomes (LEs)/lysosomes, colocalizing with the GTPases Rab7 and Rab9 and lysosome-associated membrane protein-1. We demonstrate that ORP1L interacts physically with Rab7, preferentially with its GTP-bound form, and provid...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e05-03-0189
更新日期:2005-12-01 00:00:00
abstract::Yarrowia lipolytica Pex23p and Saccharomyces cerevisiae Pex30p, Pex31p, and Pex32p comprise a family of dysferlin domain-containing peroxins. We show that the deletion of their Pichia pastoris homologues, PEX30 and PEX31, does not affect the function or division of methanol-induced peroxisomes but results in fewer and...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e07-10-1042
更新日期:2008-03-01 00:00:00
abstract::More than 97% of mice in which the C-terminal region of connexin43 (Cx43) was removed (designated as Cx43K258stop) die shortly after birth due to a defect of the epidermal barrier. The abnormal expression of Cx43K258stop protein in the uppermost layers of the epidermis seems to perturb terminal differentiation of kera...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e04-04-0324
更新日期:2004-10-01 00:00:00
abstract::Vascular endothelial (VE)-cadherin, the major adherens junction adhesion molecule in endothelial cells, interacts with p120-catenin and β-catenin through its cytoplasmic tail. However, the specific functional contributions of the catenins to the establishment of strong adhesion are not fully understood. Here we use bi...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E12-06-0471
更新日期:2013-03-01 00:00:00
abstract::The extracellular signal-regulated kinase (ERK) pathway is generally mitogenic, but, upon strong activation, it causes cell cycle arrest by a not-yet fully understood mechanism. In response to genotoxic stress, Chk1 hyperphosphorylates Cdc25A, a positive cell cycle regulator, and targets it for Skp1/Cullin1/F-box prot...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-01-0008
更新日期:2009-04-01 00:00:00
abstract::In this study, we examined the subcellular distribution and functions of LIMK1 in developing neurons. Confocal microscopy, subcellular fractionation, and expression of several epitope-tagged LIMK1 constructs revealed that LIMK1 is enriched in the Golgi apparatus and growth cones, with the LIM domain required for Golgi...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-05-0328
更新日期:2004-07-01 00:00:00
abstract::The mannose 6-phosphate (Man-6-P) lysosomal targeting signal on acid hydrolases is synthesized by the sequential action of uridine 5'-diphosphate-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase) and GlcNAc-1-phosphodiester alpha-N-acetylglucosaminidase ("unco...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-05-0398
更新日期:2009-10-01 00:00:00
abstract::The scaffold protein XB130 regulates cell growth, survival, and migration. Yeast two-hybrid screening suggests that XB130 interacts with another scaffold protein, Tks5. We hypothesized that XB130 and Tks5 form a macromolecular complex to mediate signal transduction cascades for the regulation of cell growth and surviv...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-07-0483
更新日期:2015-12-01 00:00:00
abstract::Ubiquitinated integral membrane proteins are delivered to the interior of the lysosome/vacuole for degradation. This process relies on specific ubiquitination of potential cargo and recognition of that Ub-cargo by sorting receptors at multiple compartments. We show that the endosomal Hse1-Vps27 sorting receptor binds ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e06-06-0557
更新日期:2007-01-01 00:00:00
abstract::Myosin II motors embedded within the actin cortex generate contractile forces to modulate cell shape in essential behaviors, including polarization, migration, and division. In sarcomeres, myosin II-mediated sliding of antiparallel F-actin is tightly coupled to myofibril contraction. By contrast, cortical F-actin is h...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E13-08-0450
更新日期:2014-06-15 00:00:00
abstract::Proper chromosome segregation is essential for faithful cell division and if not maintained results in defective cell function caused by the abnormal distribution of genetic information. Polo-like kinase 1-interacting checkpoint helicase (PICH) is a DNA translocase essential for chromosome bridge resolution during mit...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E20-03-0180
更新日期:2020-11-01 00:00:00
abstract::Transforming growth factor-β (TGF-β) receptor oligomerization has important roles in signaling. Complex formation among type I and type II (TβRI and TβRII) TGF-β receptors is well characterized and is essential for signal transduction. However, studies on their interactions with the type III TGF-β coreceptor (TβRIII) ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-04-0203
更新日期:2015-10-01 00:00:00
abstract::Cystic fibrosis results from mutations in the cystic fibrosis conductance regulator protein (CFTR), a cAMP/protein kinase A (PKA) and ATP-regulated Cl(-) channel. CFTR is increasingly recognized as a component of multiprotein complexes and although several inhibitory proteins to CFTR have been identified, protein comp...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e07-02-0126
更新日期:2007-09-01 00:00:00
abstract::Cellular responses to environmental changes occur on different levels. We investigated the translational response of yeast cells after mild hyperosmotic shock by isolating mRNA associated with multiple ribosomes (polysomes) followed by array analysis. Globally, recruitment of preexisting mRNAs to ribosomes (translatio...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-01-0006
更新日期:2010-09-01 00:00:00
abstract::In vitro studies suggest that the Barren protein may function as an activator of DNA topoisomerase II and/or as a component of the Xenopus condensin complex. To better understand the role of Barren in vivo, we generated conditional alleles of the structural gene for Barren (BRN1) in Saccharomyces cerevisiae. We show t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.4.1293
更新日期:2000-04-01 00:00:00
abstract::Synaptosomal associated protein of 23 kDa (SNAP-23), a plasma membrane-localized soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE), has been implicated in phagocytosis by macrophages. For elucidation of its precise role in this process, a macrophage line overexpressing monomeric Venus-tagge...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E12-01-0069
更新日期:2012-12-01 00:00:00
abstract::The late Golgi of the yeast Saccharomyces cerevisiae receives membrane traffic from the secretory pathway as well as retrograde traffic from post-Golgi compartments, but the machinery that regulates these vesicle-docking and fusion events has not been characterized. We have identified three components of a novel prote...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.1.305
更新日期:2000-01-01 00:00:00
abstract::The clinical interest in farnesyltransferase inhibitors (FTIs) makes it important to understand how these compounds affect cellular processes involving farnesylated proteins. Mitotic abnormalities observed after treatment with FTIs have so far been attributed to defects in the farnesylation of the outer kinetochore pr...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E14-11-1560
更新日期:2015-05-15 00:00:00
abstract::Multisite phosphorylation of proteins is a powerful signal processing mechanism that plays crucial roles in cell division and differentiation as well as in disease. We recently demonstrated a novel phenomenon in cell cycle regulation by showing that cyclin-dependent kinase-dependent multisite phosphorylation of a cruc...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E14-02-0774
更新日期:2014-11-05 00:00:00
abstract::Stimulation of the MAPK pathway results in mitogen- and stress-activated protein kinase 1/2 (MSK1/2)-catalyzed phosphorylation of histone H3 at serine 10 or 28 and expression of immediate-early (IE) genes. In 10T1/2 mouse fibroblasts, phosphorylation of H3S10 and H3S28 occurs on different H3 molecules and in different...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-08-0618
更新日期:2017-03-15 00:00:00
abstract::Exposure of neutrophils to chemoattractant induces cell polarization and migration. These behaviors require the asymmetric activation of distinct signaling pathways and cytoskeletal elements in the protruding pseudopod at the front of cells and the retracting uropod at the rear. An important outstanding question is, h...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e05-04-0358
更新日期:2005-12-01 00:00:00
abstract::The role of plasma membrane (PM) area as a critical factor during cell motility is poorly understood, mainly due to an inability to precisely follow PM area dynamics. To address this fundamental question, we developed static and dynamic assays to follow exocytosis, endocytosis, and PM area changes during fibroblast sp...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-01-0071
更新日期:2009-07-01 00:00:00
abstract::Glucose is a master regulator of cell behavior in the yeast Saccharomyces cerevisiae. It acts as both a metabolic substrate and a potent regulator of intracellular signaling cascades. Glucose starvation induces the transient delocalization and then partial relocalization of clathrin adaptors at the trans-Golgi network...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E12-10-0750
更新日期:2013-03-01 00:00:00
abstract::The binding of extracellular matrix proteins to integrins triggers rearrangements in the actin cytoskeleton by regulating the Rho family of small GTPases. The signaling events that mediate changes in the activity of Rho proteins in response to the extracellular matrix remain largely unknown. We have demonstrated in pr...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.12.9.2711
更新日期:2001-09-01 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