scholarly journals More than a mere supply of monomers: G-Actin pools regulate actin dynamics in dendritic spines

2017 ◽  
Vol 216 (8) ◽  
pp. 2255-2257 ◽  
Author(s):  
Katalin Schlett
Keyword(s):  
Plasma Membrane ◽  
Dendritic Spines ◽  
Actin Polymerization ◽  
Synaptic Activity ◽  
Actin Dynamics ◽  
Actin Monomer ◽  
Cell Biol ◽  
Local Enrichment

Synaptic activity reshapes the morphology of dendritic spines via regulating F-actin arborization. In this issue, Lei et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612042) reports a novel, G-actin–dependent regulation of actin polymerization within spine heads. They show that actin monomer levels are elevated in spines upon activity, with G-actin immobilized by the local enrichment of phosphatidylinositol (3,4,5)-triphosphate (PIP3) within the spine plasma membrane.

scholarly journals Neph1 Cooperates with Nephrin To Transduce a Signal That Induces Actin Polymerization

2007 ◽  
Vol 27 (24) ◽  
pp. 8698-8712 ◽  
Author(s):  
Puneet Garg ◽  
Rakesh Verma ◽  
Deepak Nihalani ◽  
Duncan B. Johnstone ◽  
Lawrence B. Holzman
Keyword(s):  
Plasma Membrane ◽  
Actin Polymerization ◽  
Intercellular Junction ◽  
Actin Dynamics ◽  
Cellular Motility ◽  
Tyrosine Residues ◽  
Signaling Complex ◽  
Direct Assembly ◽  
Junction Formation ◽  
Unique Model

ABSTRACT While the mechanisms that regulate actin dynamics in cellular motility are intensively studied, relatively little is known about signaling events that transmit outside-in signals and direct assembly and regulation of actin polymerization complexes at the cell membrane. The kidney podocyte provides a unique model for investigating these mechanisms since deletion of Nephrin or Neph1, two interacting components of the specialized podocyte intercellular junction, results in abnormal podocyte morphogenesis and junction formation. We provide evidence that extends the existing model by which the Nephrin-Neph1 complex transduces phosphorylation-mediated signals that assemble an actin polymerization complex at the podocyte intercellular junction. Upon engagement, Neph1 is phosphorylated on specific tyrosine residues by Fyn, which results in the recruitment of Grb2, an event that is necessary for Neph1-induced actin polymerization at the plasma membrane. Importantly, Neph1 and Nephrin directly interact and, by juxtaposing Grb2 and Nck1/2 at the membrane following complex activation, cooperate to augment the efficiency of actin polymerization. These data provide evidence for a mechanism reminiscent of that employed by vaccinia virus and other pathogens, by which a signaling complex transduces an outside-in signal that results in actin filament polymerization at the plasma membrane.

scholarly journals Regulated Exocytosis in Neuroendocrine Cells: A Role for Subplasmalemmal Cdc42/N-WASP-induced Actin Filaments

2004 ◽  
Vol 15 (2) ◽  
pp. 520-531 ◽  
Author(s):  
Stéphane Gasman ◽  
Sylvette Chasserot-Golaz ◽  
Magali Malacombe ◽  
Michael Way ◽  
Marie-France Bader
Keyword(s):  
Plasma Membrane ◽  
Membrane Trafficking ◽  
Actin Polymerization ◽  
Cell Activation ◽  
Secretory Granules ◽  
Small Gtpases ◽  
Neuroendocrine Cells ◽  
Actin Dynamics ◽  
Cell Periphery ◽  
Regulated Exocytosis

In neuroendocrine cells, actin reorganization is a prerequisite for regulated exocytosis. Small GTPases, Rho proteins, represent potential candidates coupling actin dynamics to membrane trafficking events. We previously reported that Cdc42 plays an active role in regulated exocytosis in chromaffin cells. The aim of the present work was to dissect the molecular effector pathway integrating Cdc42 to the actin architecture required for the secretory reaction in neuroendocrine cells. Using PC12 cells as a secretory model, we show that Cdc42 is activated at the plasma membrane during exocytosis. Expression of the constitutively active Cdc42L61 mutant increases the secretory response, recruits neural Wiskott-Aldrich syndrome protein (N-WASP), and enhances actin polymerization in the subplasmalemmal region. Moreover, expression of N-WASP stimulates secretion by a mechanism dependent on its ability to induce actin polymerization at the cell periphery. Finally, we observed that actin-related protein-2/3 (Arp2/3) is associated with secretory granules and that it accompanies granules to the docking sites at the plasma membrane upon cell activation. Our results demonstrate for the first time that secretagogue-evoked stimulation induces the sequential ordering of Cdc42, N-WASP, and Arp2/3 at the interface between granules and the plasma membrane, thereby providing an actin structure that makes the exocytotic machinery more efficient.

scholarly journals Hippocampal Dendritic Spines Are Segregated Depending on Their Actin Polymerization

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Nuria Domínguez-Iturza ◽  
María Calvo ◽  
Marion Benoist ◽  
José Antonio Esteban ◽  
Miguel Morales
Keyword(s):  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Actin Polymerization ◽  
Close Contact ◽  
Postsynaptic Membrane ◽  
Actin Dynamics ◽  
Filamentous Actin ◽  
Virtual Absence ◽  
Spine Shape ◽  
Mobile Fraction

Dendritic spines are mushroom-shaped protrusions of the postsynaptic membrane. Spines receive the majority of glutamatergic synaptic inputs. Their morphology, dynamics, and density have been related to synaptic plasticity and learning. The main determinant of spine shape is filamentous actin. Using FRAP, we have reexamined the actin dynamics of individual spines from pyramidal hippocampal neurons, both in cultures and in hippocampal organotypic slices. Our results indicate that, in cultures, the actin mobile fraction is independently regulated at the individual spine level, and mobile fraction values do not correlate with either age or distance from the soma. The most significant factor regulating actin mobile fraction was the presence of astrocytes in the culture substrate. Spines from neurons growing in the virtual absence of astrocytes have a more stable actin cytoskeleton, while spines from neurons growing in close contact with astrocytes show a more dynamic cytoskeleton. According to their recovery time, spines were distributed into two populations with slower and faster recovery times, while spines from slice cultures were grouped into one population. Finally, employing fast lineal acquisition protocols, we confirmed the existence of loci with high polymerization rates within the spine.

scholarly journals Local palmitoylation cycles define activity-regulated postsynaptic subdomains

2013 ◽  
Vol 202 (1) ◽  
pp. 145-161 ◽  
Author(s):  
Yuko Fukata ◽  
Ariane Dimitrov ◽  
Gaelle Boncompain ◽  
Ole Vielemeyer ◽  
Franck Perez ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Dendritic Spines ◽  
Recombinant Antibody ◽  
Super Resolution ◽  
Live Cell ◽  
Synaptic Activity ◽  
Membrane Targeting ◽  
Resolution Imaging

Distinct PSD-95 clusters are primary landmarks of postsynaptic densities (PSDs), which are specialized membrane regions for synapses. However, the mechanism that defines the locations of PSD-95 clusters and whether or how they are reorganized inside individual dendritic spines remains controversial. Because palmitoylation regulates PSD-95 membrane targeting, we combined a conformation-specific recombinant antibody against palmitoylated PSD-95 with live-cell super-resolution imaging and discovered subsynaptic nanodomains composed of palmitoylated PSD-95 that serve as elementary units of the PSD. PSD-95 in nanodomains underwent continuous de/repalmitoylation cycles driven by local palmitoylating activity, ensuring the maintenance of compartmentalized PSD-95 clusters within individual spines. Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation. Furthermore, changes in synaptic activity rapidly reorganized PSD-95 nano-architecture through plasma membrane–inserted DHHC2. Thus, the first genetically encoded antibody sensitive to palmitoylation reveals an instructive role of local palmitoylation machinery in creating activity-responsive PSD-95 nanodomains, contributing to the PSD (re)organization.

scholarly journals ER–mitochondria contacts: Actin dynamics at the ER control mitochondrial fission via calcium release

2017 ◽  
Vol 217 (1) ◽  
pp. 15-17 ◽  
Author(s):  
Janos Steffen ◽  
Carla M. Koehler
Keyword(s):  
Endoplasmic Reticulum ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Calcium Uptake ◽  
Calcium Release ◽  
Mitochondrial Fission ◽  
Actin Dynamics ◽  
Mitochondrial Division ◽  
Cell Biol ◽  
Important Player

The formin-like protein INF2 is an important player in the polymerization of actin filaments. In this issue, Chakrabarti et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201709111) demonstrate that INF2 mediates actin polymerization at the endoplasmic reticulum (ER), resulting in increased ER–mitochondria contacts, calcium uptake by mitochondria, and mitochondrial division.

Impaired actin dynamics and suppression of Shank2-mediated spine enlargement in cortactin knockout mice

Microscopy ◽  
2020 ◽  
Vol 69 (1) ◽  
pp. 44-52
Author(s):  
Shinji Tanaka ◽  
Yasutaka Masuda ◽  
Akihiro Harada ◽  
Shigeo Okabe
Keyword(s):  
Dendritic Spines ◽  
Actin Polymerization ◽  
Postsynaptic Density ◽  
Time Lapse ◽  
Suppressive Effect ◽  
Actin Dynamics ◽  
Spine Morphology ◽  
Actin Organization ◽  
Actin Turnover ◽  
Time Lapse Imaging

Abstract Cortactin regulates actin polymerization and stabilizes branched actin network. In neurons, cortactin is enriched in dendritic spines that contain abundant actin polymers. To explore the function of cortactin in dendritic spines, we examined spine morphology and dynamics in cultured neurons taken from cortactin knockout (KO) mice. Histological analysis revealed that the density and morphology of dendritic spines were not significantly different between wild-type (WT) and cortactin KO neurons. Time-lapse imaging of hippocampal slice cultures showed that the extent of spine volume change was similar between WT and cortactin KO neurons. Despite little effect of cortactin deletion on spine morphology and dynamics, actin turnover in dendritic spines was accelerated in cortactin KO neurons. Furthermore, we detected a suppressive effect of cortactin KO on spine head size under the condition of excessive spine enlargement induced by overexpression of a prominent postsynaptic density protein Shank2. These results suggest that cortactin may have a role in maintaining actin organization by stabilizing actin filaments near the postsynaptic density.

scholarly journals Regulation of Sodium Channel Activity by Capping of Actin Filaments

2003 ◽  
Vol 14 (4) ◽  
pp. 1709-1716 ◽  
Author(s):  
Ekaterina V. Shumilina ◽  
Yuri A. Negulyaev ◽  
Elena A. Morachevskaya ◽  
Horst Hinssen ◽  
Sofia Yu Khaitlina
Keyword(s):  
Plasma Membrane ◽  
Sodium Channel ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
Channel Activity ◽  
Capping Protein ◽  
Channel Inactivation ◽  
Actin Capping Protein ◽  
Actin Capping

Ion transport in various tissues can be regulated by the cortical actin cytoskeleton. Specifically, involvement of actin dynamics in the regulation of nonvoltage-gated sodium channels has been shown. Herein, inside-out patch clamp experiments were performed to study the effect of the heterodimeric actin capping protein CapZ on sodium channel regulation in leukemia K562 cells. The channels were activated by cytochalasin-induced disruption of actin filaments and inactivated by G-actin under ionic conditions promoting rapid actin polymerization. CapZ had no direct effect on channel activity. However, being added together with G-actin, CapZ prevented actin-induced channel inactivation, and this effect occurred at CapZ/actin molar ratios from 1:5 to 1:100. When actin was allowed to polymerize at the plasma membrane to induce partial channel inactivation, subsequent addition of CapZ restored the channel activity. These results can be explained by CapZ-induced inhibition of further assembly of actin filaments at the plasma membrane due to the modification of actin dynamics by CapZ. No effect on the channel activity was observed in response to F-actin, confirming that the mechanism of channel inactivation does not involve interaction of the channel with preformed filaments. Our data show that actin-capping protein can participate in the cytoskeleton-associated regulation of sodium transport in nonexcitable cells.

scholarly journals Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis

2009 ◽  
Vol 185 (2) ◽  
pp. 323-339 ◽  
Author(s):  
Pirta Hotulainen ◽  
Olaya Llano ◽  
Sergei Smirnov ◽  
Kimmo Tanhuanpää ◽  
Jan Faix ◽  
...  
Keyword(s):  
Actin Filament ◽  
Dendritic Spines ◽  
Actin Polymerization ◽  
Morphological Changes ◽  
Small Gtpase ◽  
Actin Dynamics ◽  
Excitatory Synapses ◽  
Mature Brain ◽  
Key Steps ◽  
Spine Morphogenesis

Dendritic spines are small protrusions along dendrites where the postsynaptic components of most excitatory synapses reside in the mature brain. Morphological changes in these actin-rich structures are associated with learning and memory formation. Despite the pivotal role of the actin cytoskeleton in spine morphogenesis, little is known about the mechanisms regulating actin filament polymerization and depolymerization in dendritic spines. We show that the filopodia-like precursors of dendritic spines elongate through actin polymerization at both the filopodia tip and root. The small GTPase Rif and its effector mDia2 formin play a central role in regulating actin dynamics during filopodia elongation. Actin filament nucleation through the Arp2/3 complex subsequently promotes spine head expansion, and ADF/cofilin-induced actin filament disassembly is required to maintain proper spine length and morphology. Finally, we show that perturbation of these key steps in actin dynamics results in altered synaptic transmission.

scholarly journals Lysosomes convene to keep the synapse clean

2017 ◽  
Vol 216 (8) ◽  
pp. 2251-2253 ◽  
Author(s):  
Natalia L. Kononenko
Keyword(s):  
Plasma Membrane ◽  
Protein Degradation ◽  
Neuronal Activity ◽  
Dendritic Spines ◽  
Acid Receptor ◽  
Synaptic Remodeling ◽  
Cell Biol ◽  
First Time ◽  
Local Protein

In neurons, lysosomes regulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor levels at the plasma membrane, although their presence at distal dendrites is controversial. In this issue, Goo et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201704068) show for the first time that neuronal activity positions lysosomes at the dendritic spines to facilitate synaptic remodeling through local protein degradation.

scholarly journals Phosphoinositide-dependent enrichment of actin monomers in dendritic spines regulates synapse development and plasticity

2017 ◽  
Vol 216 (8) ◽  
pp. 2551-2564 ◽  
Author(s):  
Wenliang Lei ◽  
Kenneth R. Myers ◽  
Yanfang Rui ◽  
Siarhei Hladyshau ◽  
Denis Tsygankov ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Neurological Disorders ◽  
Synaptic Activity ◽  
Excitatory Synapses ◽  
Synapse Development ◽  
Actin Monomer ◽  
Actin Remodeling ◽  
Vertebrate Brain ◽  
Spine Development

Dendritic spines are small postsynaptic compartments of excitatory synapses in the vertebrate brain that are modified during learning, aging, and neurological disorders. The formation and modification of dendritic spines depend on rapid assembly and dynamic remodeling of the actin cytoskeleton in this highly compartmentalized space, but the precise mechanisms remain to be fully elucidated. In this study, we report that spatiotemporal enrichment of actin monomers (G-actin) in dendritic spines regulates spine development and plasticity. We first show that dendritic spines contain a locally enriched pool of G-actin that can be regulated by synaptic activity. We further find that this G-actin pool functions in spine development and its modification during synaptic plasticity. Mechanistically, the relatively immobile G-actin pool in spines depends on the phosphoinositide PI(3,4,5)P3 and involves the actin monomer–binding protein profilin. Together, our results have revealed a novel mechanism by which dynamic enrichment of G-actin in spines regulates the actin remodeling underlying synapse development and plasticity.

Sign in / Sign up

Export Citation Format

Share Document