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51.
LIM kinase 1 and cofilin regulate actin filament population required for dynamin-dependent apical carrier fission from the trans-Golgi network 总被引:1,自引:0,他引:1
Salvarezza SB Deborde S Schreiner R Campagne F Kessels MM Qualmann B Caceres A Kreitzer G Rodriguez-Boulan E 《Molecular biology of the cell》2009,20(1):438-451
The functions of the actin cytoskeleton in post-Golgi trafficking are still poorly understood. Here, we report the role of LIM Kinase 1 (LIMK1) and its substrate cofilin in the trafficking of apical and basolateral proteins in Madin-Darby canine kidney cells. Our data indicate that LIMK1 and cofilin organize a specialized population of actin filaments at the Golgi complex that is selectively required for the emergence of an apical cargo route to the plasma membrane (PM). Quantitative pulse-chase live imaging experiments showed that overexpression of kinase-dead LIMK1 (LIMK1-KD), or of LIMK1 small interfering RNA, or of an activated cofilin mutant (cofilin S3A), selectively slowed down the exit from the trans-Golgi network (TGN) of the apical PM marker p75-green fluorescent protein (GFP) but did not interfere with the apical PM marker glycosyl phosphatidylinositol-YFP or the basolateral PM marker neural cell adhesion molecule-GFP. High-resolution live imaging experiments of carrier formation and release by the TGN and analysis of peri-Golgi actin dynamics using photoactivatable GFP suggest a scenario in which TGN-localized LIMK1-cofilin regulate a population of actin filaments required for dynamin-syndapin-cortactin–dependent generation and/or fission of precursors to p75 transporters. 相似文献
52.
Wang D Tan YC Kreitzer GE Nakai Y Shan D Zheng Y Huang XY 《The Journal of biological chemistry》2006,281(43):32660-32667
Growth factors induce massive actin cytoskeletal remodeling in cells. These reorganization events underlie various cellular responses such as cell migration and morphological changes. One major form of actin reorganization is the formation and disassembly of dorsal ruffles (also named waves, dorsal rings, or circular ruffles). Dorsal ruffles are involved in physiological functions including cell migration, invasion, macropinocytosis, plasma membrane recycling, and others. Growth factors initiate rapid formation (within 5 min) of circular membrane ruffles, and these ruffles move along the dorsal side of the cells, constrict, close, and eventually disassemble ( approximately 20 min). Considerable attention has been devoted to the mechanism by which growth factors induce the formation of dorsal ruffles. However, little is known of the mechanism by which these ruffles are disassembled. Here we have shown that G proteins G(12) and G(13) control the rate of disassembly of dorsal ruffles. In Galpha(12)(-/-)Galpha(13)(-/-) fibroblast cells, dorsal ruffles induced by growth factor treatment remain visible substantially longer ( approximately 60 min) than in wild-type cells, whereas the rate of formation of these ruffles was the same with or without Galpha(12) and Galpha(13). Thus, Galpha(12)/Galpha(13) critically regulate dorsal ruffle turnover. 相似文献
53.
Given the pervasive influence of human induced habitat fragmentation in ecological processes, landscape models are a welcome advance. The development of GIS software has allowed a greater use of these models and of analyses of the relationship between species and habitat variables. Habitat suitability models are thus theoretical concepts that can be used for planning in fragmented landscapes and habitat conservation. The most commonly used models are based on single species and on the assignment of suitability values for some environmental variables. Generally the cartographic basis for modeling suitability are thematic maps produced by a Boolean logic. In this paper we propose a model based on a set of focal species and on maps produced by a fuzzy classification method. Focal species, selected by an expert-based approach, provide a practical way of extending the scope of habitat suitability models to the conservation of biodiversity at landscape scale. The utilisation of a classification method that applies a continuity criterion may allow more consideration of the connectivity of an area because it allows a better detection of ecological gradients within a landscape. We applied this methodology to the Tuscany region focusing on terrestrial mammals. Performing a fuzzy classification we produced five land cover maps and through image processing operations we obtained a suitability model which applies a continuity criterion. The resulting suitability fuzzy model seems better for the study of connectivity and fragmentation, especially in areas with high spatial complexity. 相似文献
54.
Bipul R. Acharya Cedric Espenel Geri Kreitzer 《The Journal of biological chemistry》2013,288(45):32302-32313
KIF17 is a kinesin-2 family motor that interacts with EB1 at microtubule (MT) plus-ends and contributes to MT stabilization in epithelial cells. The mechanism by which KIF17 affects MTs and how its activity is regulated are not yet known. Here, we show that EB1 and the KIF17 autoinhibitory tail domain (KIF17-Tail) interacted competitively with the KIF17 catalytic motor domain (K370). Both EB1 and KIF17-Tail decreased the K0.5MT of K370, with opposing effects on MT-stimulated ATPase activity. Importantly, K370 had independent effects on MT dynamic instability, resulting in formation of long MTs without affecting polymerization rate or total polymer mass. K370 also inhibited MT depolymerization induced by dilution in vitro and by nocodazole in cells, suggesting that it acts by protecting MT plus-ends. Interestingly, KIF17-Tail bound MTs and tubulin dimers, delaying initial MT polymerization in vitro and MT regrowth in cells. However, neither EB1 nor KIF17-Tail affected K370-mediated MT polymerization or stabilization significantly in vitro, and EB1 was dispensable for MT stabilization by K370 in cells. Thus, although EB1 and KIF17-Tail may coordinate KIF17 catalytic activity, our data reveal a novel and direct role for KIF17 in regulating MT dynamics. 相似文献
55.
Recent advances in optogenetics have permitted investigations of specific cell types in the nervous system with unprecedented precision and control. This review will discuss the use of optogenetic techniques in the study of mammalian neural circuitry in vivo, as well as practical and theoretical considerations in their application. 相似文献
56.
Excitatory synapses onto projection neurons in the striatum, the input nucleus of the basal ganglia, play a key role in regulating basal ganglia circuit function and are a major site of long-term synaptic plasticity. Here, we review the mechanisms and regulation of both long-term potentiation and long-term depression at these synapses. In particular, we highlight the role that neuromodulators play in determining the strength and direction of plasticity, which ultimately shapes the balance of activity in basal ganglia circuits and regulates motor behavior. 相似文献
57.
58.
Malta E Verhagen CP Moolenaar GF Filippov DV van der Marel GA Goosen N 《DNA Repair》2008,7(10):1647-1658
UvrB is the main damage recognition protein in bacterial nucleotide excision repair and is capable of recognizing various structurally unrelated types of damage. Previously we have shown that upon binding of Escherichia coli UvrB to damaged DNA two nucleotides become extrahelical: the nucleotide directly 3' to the lesion and its base-pairing partner in the non-damaged strand. Here we demonstrate using a novel fluorescent 2-aminopurine-menthol modification that the position of the damaged nucleotide itself does not change upon UvrB binding. A co-crystal structure of B. caldotenax UvrB and DNA has revealed that one nucleotide is flipped out of the DNA helix into a pocket of the UvrB protein where it stacks on Phe249 [J.J. Truglio, E. Karakas, B. Hau, H. Wang, M.J. DellaVecchia, B. van Houten, C. Kisker, Structural basis for DNA recognition and processing by UvrB, Nat. Struct. Mol. Biol. 13 (2006) 360-364]. By mutating the equivalent of Phe249 (Tyr249) in the E. coli UvrB protein we show that on damaged DNA neither of the extrahelical nucleotides is inserted into this protein pocket. The mutant UvrB protein, however, resulted in an increased binding and incision of undamaged DNA showing that insertion of a base into the nucleotide-binding pocket is important for dissociation of UvrB from undamaged sites. Replacing the nucleotides in the non-damaged strand with a C3-linker revealed that the extruded base in the non-damaged strand is not directly involved in UvrB-binding or UvrC-mediated incision, but that its displacement is needed to allow access for residues of UvrB or UvrC to the neighboring base, which is directly opposite the DNA damage. This interaction is shown to be essential for optimal 3'-incision by UvrC. After 3'-incision base flipping in the non-damaged DNA strand is lost, indicative for a conformational change needed to prepare the UvrB-DNA complex for 5'-incision. 相似文献
59.
60.
Recent studies suggest that endocannabinoids act as retrograde messengers at many synapses in the central nervous system. Activation of phospholipases, either through calcium-mediated or receptor-mediated signaling, leads to the formation and release of endocannabinoids. These lipophilic signaling molecules diffuse to nearby presynaptic terminals where they bind to specific G-protein-coupled receptors and inhibit neurotransmitter release for tens of seconds. Thus, an important physiological role of endocannabinoids may be to provide a mechanism by which neurons can rapidly regulate the strength of their synaptic inputs. 相似文献