scholarly journals Palmitoylation of LIM Kinase-1 ensures spine-specific actin polymerization and morphological plasticity

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Joju George ◽  
Cary Soares ◽  
Audrey Montersino ◽  
Jean-Claude Beique ◽  
Gareth M Thomas
Keyword(s):  
Dendritic Spine ◽  
Actin Polymerization ◽  
Structural Plasticity ◽  
Morphological Plasticity ◽  
Actin Dynamics ◽  
Lim Kinase ◽  
Lim Kinase 1 ◽  
Normal Spine ◽  
Necessary And Sufficient

Precise regulation of the dendritic spine actin cytoskeleton is critical for neurodevelopment and neuronal plasticity, but how neurons spatially control actin dynamics is not well defined. Here, we identify direct palmitoylation of the actin regulator LIM kinase-1 (LIMK1) as a novel mechanism to control spine-specific actin dynamics. A conserved palmitoyl-motif is necessary and sufficient to target LIMK1 to spines and to anchor LIMK1 in spines. ShRNA knockdown/rescue experiments reveal that LIMK1 palmitoylation is essential for normal spine actin polymerization, for spine-specific structural plasticity and for long-term spine stability. Palmitoylation is critical for LIMK1 function because this modification not only controls LIMK1 targeting, but is also essential for LIMK1 activation by its membrane-localized upstream activator PAK. These novel roles for palmitoylation in the spatial control of actin dynamics and kinase signaling provide new insights into structural plasticity mechanisms and strengthen links between dendritic spine impairments and neuropathological conditions.

scholarly journals Interaction between distinct actin pools controls activity-dependent actin dynamics in the dendritic spine

2016 ◽  
Author(s):  
Oleg O. Glebov ◽  
Juan Burrone
Keyword(s):  
Cell Line ◽  
Dendritic Spine ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
List Type ◽  
Dependent Manner ◽  
Complex Activity ◽  
Actin Depolymerization ◽  
Labile Pool

AbstractActin cytoskeleton is composed of functionally distinct pools of filamentous (F)-actin defined by their regulatory machinery and dynamics. Although these networks may compete for actin monomers and regulatory factors1–4, the interaction between them remains poorly understood. Here, we show that disruption of the labile F-actin pool in neurons by limited actin depolymerization5,6 unexpectedly triggers rapid enhancement of the F-actin content at the dendritic spine. Long-term blockade of NMDA-type receptors decreases spine actin polymerization, which is specifically restored by the labile pool ablation. Increase in the spine actin is triggered by blockade of formin-induced actin polymerization in a manner dependent on Arp2/3 complex activity. Finally, limited actin depolymerization increases F-actin levels in a cultured cell line, suggesting the generality of the two-tiered actin dynamics. Based on these findings, we propose a model whereby the labile pool of F-actin controlled by formin restricts the polymerization state of the Arp2/3-regulated stable spine actin, suggesting a feedback principle at the core of cytoskeletal organization in neurons.HighlightsDisruption of labile F-actin by limited depolymerization rapidly increases the synaptic F-actin content;The depolymerization-induced F-actin boost reverses decrease in synaptic F-actin induced by long-term NMDA receptor blockade;Blockade of formin-dependent actin polymerization boosts synaptic F-actin in an Arp2/3-dependent manner;Limited actin depolymerization enhances overall F-actin content in a mammalian cell line.

scholarly journals Author response: Palmitoylation of LIM Kinase-1 ensures spine-specific actin polymerization and morphological plasticity

2015 ◽  
Author(s):  
Joju George ◽  
Cary Soares ◽  
Audrey Montersino ◽  
Jean-Claude Beique ◽  
Gareth M Thomas
Keyword(s):  
Actin Polymerization ◽  
Morphological Plasticity ◽  
Author Response ◽  
Lim Kinase ◽  
Lim Kinase 1

scholarly journals LIM Kinase 1 and Cofilin Regulate Actin Filament Population Required for Dynamin-dependent Apical Carrier Fission from the Trans-Golgi Network

2009 ◽  
Vol 20 (1) ◽  
pp. 438-451 ◽  
Author(s):  
Susana B. Salvarezza ◽  
Sylvie Deborde ◽  
Ryan Schreiner ◽  
Fabien Campagne ◽  
Michael M. Kessels ◽  
...  
Keyword(s):  
Actin Filaments ◽  
Fluorescent Protein ◽  
Live Imaging ◽  
Actin Dynamics ◽  
Lim Kinase ◽  
Trans Golgi Network ◽  
Lim Kinase 1 ◽  
Photoactivatable Gfp ◽  
Green Fluorescent ◽  
Golgi Network

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.

scholarly journals Endophilin A1 promotes Actin Polymerization in response to Ca2+/calmodulin to Initiate Structural Plasticity of Dendritic Spines

2020 ◽  
Author(s):  
Yanrui Yang ◽  
Jiang Chen ◽  
Xue Chen ◽  
Di Li ◽  
Jianfeng He ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Actin Polymerization ◽  
Morphological Changes ◽  
Structural Plasticity ◽  
Long Term Potentiation ◽  
Membrane Dynamics ◽  
Long Term Memory ◽  
Induction Phase ◽  
Term Potentiation

AbstractDendritic spines of excitatory neurons undergo activity-dependent structural and functional plasticity, which are cellular correlates of learning and memory. However, mechanisms underlying the rapid morphological changes immediately after NMDAR-mediated Ca2+ influx into spines remain poorly understood. Here we report that endophilin A1, a neuronal N-BAR protein, orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in the induction phase of long-term potentiation (LTP). Upon LTP induction, Ca2+/calmodulin enhances its binding to both membrane and p140Cap, a cytoskeleton regulator. As a result, endophilin A1 rapidly associates with the relaxed plasma membrane and promotes actin polymerization, leading to acute expansion of spine head. Moreover, not only the p140Cap-binding, but also calmodulin- and membrane-binding capacities of endophilin A1 are required for LTP and long-term memory. Thus, endophilin A1 functions as calmodulin effector to drive spine enlargement in response to Ca2+ influx in the initial phase of structural plasticity.

scholarly journals Endophilin A1 drives acute structural plasticity of dendritic spines in response to Ca2+/calmodulin

2021 ◽  
Vol 220 (6) ◽  
Author(s):  
Yanrui Yang ◽  
Jiang Chen ◽  
Xue Chen ◽  
Di Li ◽  
Jianfeng He ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Dendritic Spines ◽  
Actin Polymerization ◽  
Structural Plasticity ◽  
Long Term Potentiation ◽  
Membrane Dynamics ◽  
Long Term Memory ◽  
Term Memory ◽  
Term Potentiation

Induction of long-term potentiation (LTP) in excitatory neurons triggers a large transient increase in the volume of dendritic spines followed by decays to sustained size expansion, a process termed structural LTP (sLTP) that contributes to the cellular basis of learning and memory. Although mechanisms regulating the early and sustained phases of sLTP have been studied intensively, how the acute spine enlargement immediately after LTP stimulation is achieved remains elusive. Here, we report that endophilin A1 orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in NMDAR-mediated LTP. Upon LTP induction, Ca2+/calmodulin enhances binding of endophilin A1 to both membrane and p140Cap, a cytoskeletal regulator. Consequently, endophilin A1 rapidly localizes to the plasma membrane and recruits p140Cap to promote local actin polymerization, leading to spine head expansion. Moreover, its molecular functions in activity-induced rapid spine growth are required for LTP and long-term memory. Thus, endophilin A1 serves as a calmodulin effector to drive acute structural plasticity necessary for learning and memory.

scholarly journals LIM kinase 1 - dependent cofilin 1 pathway and actin dynamics mediate nuclear retinoid receptor function in T lymphocytes

2011 ◽  
Vol 12 (1) ◽  
pp. 41 ◽  
Author(s):  
Mohammad Ishaq ◽  
Bor-Ruei Lin ◽  
Marjorie Bosche ◽  
Xin Zheng ◽  
Jun Yang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Actin Dynamics ◽  
Receptor Function ◽  
Retinoid Receptor ◽  
Lim Kinase ◽  
Lim Kinase 1

scholarly journals Correction: LIM kinase 1 - dependent cofilin 1 pathway and actin dynamics mediate nuclear retinoid receptor function in T lymphocytes

2012 ◽  
Vol 13 (1) ◽  
pp. 14
Author(s):  
Mohammad Ishaq ◽  
Bor-Ruei Lin ◽  
Marjorie Bosche ◽  
Xin Zheng ◽  
Jun Yang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Actin Dynamics ◽  
Receptor Function ◽  
Retinoid Receptor ◽  
Lim Kinase ◽  
Lim Kinase 1

scholarly journals Abi2-Deficient Mice Exhibit Defective Cell Migration, Aberrant Dendritic Spine Morphogenesis, and Deficits in Learning and Memory

2004 ◽  
Vol 24 (24) ◽  
pp. 10905-10922 ◽  
Author(s):  
Matthew Grove ◽  
Galina Demyanenko ◽  
Asier Echarri ◽  
Patricia A. Zipfel ◽  
Marisol E. Quiroz ◽  
...  
Keyword(s):  
Cell Migration ◽  
Dendritic Spine ◽  
Actin Polymerization ◽  
Adherens Junctions ◽  
Actin Dynamics ◽  
Long Term Memory ◽  
Cell Morphogenesis ◽  
And Migration

ABSTRACT The Abl-interactor (Abi) family of adaptor proteins has been linked to signaling pathways involving the Abl tyrosine kinases and the Rac GTPase. Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. Here we demonstrate that Abi2 modulates cell morphogenesis and migration in vivo. Homozygous deletion of murine abi2 produced abnormal phenotypes in the eye and brain, the tissues with the highest Abi2 expression. In the absence of Abi2, secondary lens fiber orientation and migration were defective in the eye, without detectable defects in proliferation, differentiation, or apoptosis. These phenotypes were consistent with the localization of Abi2 at adherens junctions in the developing lens and at nascent epithelial cell adherens junctions in vitro. Downregulation of Abi expression by RNA interference impaired adherens junction formation and correlated with downregulation of the Wave actin-nucleation promoting factor. Loss of Abi2 also resulted in cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. These findings support a role for Abi2 in the regulation of cytoskeletal dynamics at adherens junctions and dendritic spines, which is critical for intercellular connectivity, cell morphogenesis, and cognitive functions.

scholarly journals LIM kinase-1 selectively promotes glycoprotein Ib-IX–mediated TXA2 synthesis, platelet activation, and thrombosis

Blood ◽  
2013 ◽  
Vol 121 (22) ◽  
pp. 4586-4594 ◽  
Author(s):  
Brian Estevez ◽  
Aleksandra Stojanovic-Terpo ◽  
M. Keegan Delaney ◽  
Kelly A. O’Brien ◽  
Michael C. Berndt ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Arterial Thrombosis ◽  
Actin Polymerization ◽  
Glycoprotein Ib ◽  
Lim Kinase ◽  
Lim Kinase 1 ◽  
Cpla2 Activation ◽  
Key Points

Key Points Role for LIMK1 in GPIb-IX–dependent cPLA2 activation, TXA2 synthesis, and platelet activation independent of its role in actin polymerization. LIMK1 is important in arterial thrombosis in vivo but appears to be dispensable for hemostasis, suggesting a new antithrombotic target.

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