Abstract：
:Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson’s disease, but the precise physiological function of the protein remains ill-defined. Recently, our group proposed a model in which LRRK2 kinase activity is part of an EndoA phosphorylation cycle that facilitates efficient vesicle formation at synapses in the Drosophila melanogaster neuromuscular junctions.Flies harbor only one Lrrk gene, which might encompass the functions of both mammalian LRRK1 and LRRK2. We therefore studied the role of LRRK2 in mammalian synaptic function and provide evidence that knockout or pharmacological inhibition of LRRK2 results in defects in synaptic vesicle endocytosis, altered synaptic morphology and impairments in neurotransmission. In addition, our data indicate that mammalian endophilin A1 (EndoA1,also known as SH3GL2) is phosphorylated by LRRK2 in vitro at T73 and S75, two residues in the BAR domain. Hence, our results indicate that LRRK2 kinase activity has an important role in the regulation of clathrin-mediated endocytosis of synaptic vesicles and subsequent neurotransmission at the synapse.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Arranz AM,Delbroek L,Van Kolen K,Guimarães MR,Mandemakers W,Daneels G,Matta S,Calafate S,Shaban H,Baatsen P,De Bock PJ,Gevaert K,Vanden Berghe P,Verstreken P,De Strooper B,Moechars Ddoi
10.1242/jcs.158196subject
Has Abstractpub_date
2015-02-01 00:00:00pages
541–52issue
3eissn
0021-9533issn
1477-9137pii
jcs.158196journal_volume
128pub_type
杂志文章abstract：:The cell wall of 24-h zygotes of Fucus serratus is composed of 3 layers--an inner fibrillar layer (sulphated fucan), an outer fibrillar layer (alginic aicd/cellulose) and an exterior amorphous layer (sulphated fucan, alginic acid). The 2 layers containing sulphated fucan are preferentially thickened at the rhizoid pol...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-08-01 00:00:00
abstract：:A comparison of stained cytosolic proteins, in vivo 80 S ribosome translation products and in vitro translation products of poly(A)+ RNA from three species of Acetabularia was performed after characterization of their molecular weights and isoelectric points via two-dimensional electrophoresis. A total of 803 stained ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:Actin-based myosin motors have a pivotal role in intracellular trafficking in eukaryotic cells. The parasitic protozoan organism Leishmania expresses a novel class of myosin, myosin XXI (Myo21), which is preferentially localized at the proximal region of the flagellum. However, its function in this organism remains la...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.064725
更新日期：2010-06-15 00:00:00
abstract：:Fine-tuning of NMDA glutamatergic receptor signalling strategically controls crucial brain functions. This process depends on several ligands and modulators, one of which unexpectedly includes the serine protease tissue-type plasminogen activator (tPA). In vitro, tPA increases NMDA-receptor-mediated calcium influx by ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03354
更新日期：2007-02-15 00:00:00
abstract：:Epithelial junctions depend on intercellular interactions between β(1) subunits of the Na(+)/K(+)-ATPase molecules of neighboring cells. The interaction between dog and rat subunits is less effective than the interaction between two dog β(1) subunits, indicating the importance of species-specific regions for β(1)-β(1)...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.100149
更新日期：2012-03-15 00:00:00
abstract：:It is now becoming clear that additional transmembrane components can modify integrin-mediated adhesion. Syndecan-4 is a transmembrane heparan sulfate proteoglycan whose external glycosaminoglycan chains can bind extracellular matrix ligands and whose core protein cytoplasmic domain can signal during adhesion. Two pap...
journal_title：Journal of cell science
pub_type： 评论,杂志文章,评审
doi：
更新日期：1999-10-01 00:00:00
abstract：:Polypeptide chains synthesized by membrane-bound ribosomes are translocated through, and integrated into, the endoplasmic reticulum (ER) membrane by means of the protein translocation channel, the translocon. Positive charges on the nascent chain determine the orientation of the hydrophobic segment as it is inserted i...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.086850
更新日期：2011-12-15 00:00:00
abstract：:Desmosomes are intercellular junctions specialised for strong adhesion that are prominent in the epidermis and heart muscle. Defective desmosomal function due to inherited mutations in the constitutive desmosomal gene desmoplakin (DSP) causes skin or heart disorders and in some instances both. Different mutations have...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.084152
更新日期：2012-06-15 00:00:00
abstract：:Endocytosis of chemokine receptors regulates signal transduction initiated by chemokines, but the molecular mechanisms underlying this process are not fully defined. In this work, we assessed the involvement of the motor protein nonmuscle myosin heavy chain IIA (MIIA) in the endocytosis of CXCR4 induced by SDF-1alpha ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03415
更新日期：2007-03-15 00:00:00
abstract：:Hepatocyte growth factor (HGF)/scatter factor modulates the motility of HT29 colon carcinoma cells in vitro by inducing morphological changes that depend on the type of extra-cellular matrix (ECM) ligand; HGF-induced scattering of HT29 cells is observed if cells are grown on plastic coated with serum proteins but not ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:Regulation of cell-cell contacts is essential for integrity of the vascular endothelium. Here, a critical role of the F-actin-binding protein drebrin in maintaining endothelial integrity is revealed under conditions mimicking vascular flow. Drebrin knockdown leads to weakening of cell-cell contacts, characterized by l...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.129437
更新日期：2013-08-15 00:00:00
abstract：:The relationshio between Con A-receptor mobility and Con A-induced agglutination of Novikoff hepatoma and normal rat liver cells was investigated. Novikoff cells, incubated with fluorescein-labelled Con A at 3 degrees C displayed uniform, ring-like surface fluorescence. Increasing the temperature of the cells to 37 de...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-04-01 00:00:00
abstract：:Dynamin, a microtubule-activated GTPase, has recently been identified as the product of the shibire gene in Drosophila. shi(ts) mutants are defective in synaptic vesicle recycling, which leads to rapid and reversible temperature-sensitive paralysis. In the present study, results from RNase protection assays and analys...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:Although membrane addition is crucial for cytokinesis in many animal cell types, the specific mechanisms supporting cleavage furrow ingression are not yet understood. Mutations in the gene brunelleschi (bru), which encodes the Drosophila ortholog of the yeast Trs120p subunit of TRAPPII, cause failure of furrow ingress...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.054536
更新日期：2009-12-15 00:00:00
abstract：:In the developing Drosophila eye, the centrioles of the differentiating retinal cells are not surrounded by the microtubule-nucleating γ-tubulin, suggesting that they are unable to organize functional microtubule-organizing centers. Consistent with this idea, Cnn and Spd-2, which are involved in γ-tubulin recruitment,...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.211441
更新日期：2018-02-22 00:00:00
abstract：:Myosin VI is an actin-based retrograde motor protein that plays a crucial role in both endocytic and secretory membrane trafficking pathways. Myosin VI's targeting to and function in these intracellular pathways is mediated by a number of specific binding partners. In this paper we have identified a new myosin-VI-bind...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.014217
更新日期：2007-12-15 00:00:00
abstract：:Cystogenesis is a morphological consequence of numerous genetic diseases of the epithelium. In the kidney, the pathogenic mechanisms underlying the program of altered cell and tubule morphology are obscured by secondary effects of cyst expansion. Here, we developed a new 3D tubuloid system to isolate the rapid changes...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.249557
更新日期：2020-07-16 00:00:00
abstract：:Toxoplasma gondii is an obligate intracellular parasite that infects a wide variety of vertebrate cells including macrophages. We have used a combination of video microscopy and fluorescence localization to examine the entry of Toxoplasma into macrophages and nonphagocytic host cells. Toxoplasma actively invaded host ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
abstract：:CDC14 was originally identified by L. Hartwell in his famous screen for genes that regulate the budding yeast cell cycle. Subsequent work showed that Cdc14 belongs to a family of highly conserved dual-specificity phosphatases that are present in a wide range of organisms from yeast to human. Human CDC14B is even able ...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.074815
更新日期：2010-09-01 00:00:00
abstract：:Microinjection of a bacterially expressed, TRITC labelled fragment of the centrosome-associated protein CP190 of Drosophila melanogaster, into syncytial Drosophila embryos, shows it to associate with the centrosomes during mitosis, and to relocate to chromatin during interphase. Indirect immunofluorescence staining of...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:Lysosomal cysteine proteases from mammalian cells and plants are regulated by endogenous tight-binding inhibitors from the cystatin superfamily. The presence of cystatin-like inhibitors in lower eukaryotes such as protozoan parasites has not yet been demonstrated, although these cells express large quantities of cyste...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-11-01 00:00:00
abstract：:Phagocytosis is an actin-based process used by macrophages to clear particles greater than 0.5 microm in diameter. In addition to its role in immunological responses, phagocytosis is also necessary for tissue remodeling and repair. To prevent catastrophic autoimmune reactions, phagocytosis must be tightly regulated. I...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-02-15 00:00:00
abstract：:Maternally inherited cytoplasmic bacteria have occasionally been observed in embryos and adults of different strains of several Drosophila species. While there is a considerable body of data on the relationship between bacteria and embryo viability, little is known about the behavior of these bacteria during the early...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:Abnormal cardiac valve morphogenesis is a common cause of human congenital heart disease. The molecular mechanisms regulating endocardial cell proliferation and differentiation into cardiac valves remain largely unknown, although great progress has been made on the endocardial contribution to the atrioventricular cush...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.116996
更新日期：2013-03-15 00:00:00
abstract：:Traction forces increase after microtubule depolymerization; however, the signaling mechanisms underlying this, in particular the dependence upon myosin II, remain unclear. We investigated the mechanism of traction force increase after nocodazole-induced microtubule depolymerization by applying traction force microsco...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.090563
更新日期：2011-12-15 00:00:00
abstract：:Integrins play a key role in regulating endothelial cell survival, migration and differentiated function during angiogenic blood-vessel remodeling. Integrin-linked kinase (ILK) is a multidomain protein that interacts with the cytoplasmic tail of integrin beta subunits and is thought to participate in integrin-mediated...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01331
更新日期：2004-09-01 00:00:00
abstract：:The distribution of centromeres in the interphase nuclei of human diploid fibroblasts was analyzed using anti-centromere immunofluorescence and laser scanning confocal microscopoy. The positions of the centromeres were placed within the nuclear chromatin distribution and presented some aspects of the dynamics of nucle...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-06-01 00:00:00
abstract：:The establishment of a tissue-culture system for epithelial cells derived from human foetal pancreas has recently been reported. Further analyses have now been made on these cells in vitro, together with parallel investigation of the distribution of different cell types within the intact foetal pancreas. Results suppo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
abstract：:The existence of two forms of the chromosome passenger complex (CPC) in the mammalian oocyte has meant that its role in female meiosis has remained unclear. Here we use loss- and gain-of function approaches to assess the meiotic functions of one of the shared components of these complexes, INCENP, and of the variable ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.067447
更新日期：2010-12-15 00:00:00
abstract：:Inactivation of the transcription factor and tumor suppressor p53, and overexpression or mutational activation of PIK3CA, which encodes the p110alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), are two of the most common deleterious genomic changes in cancer, including in ovarian carcinomas. We investig...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.013029
更新日期：2008-03-01 00:00:00
