共查询到20条相似文献,搜索用时 578 毫秒
1.
Yun Hyun Huh So Hee Kim Kyoung-Hwun Chung Sena Oh Min-Sung Kwon Hyun-Woo Choi Sangmyung Rhee Je-Hwang Ryu Zee Yong Park Chang-Duk Jun Woo Keun Song 《Cellular and molecular life sciences : CMLS》2013,70(24):4841-4854
Membrane protrusions, like lamellipodia, and cell movement are dependent on actin dynamics, which are regulated by a variety of actin-binding proteins acting cooperatively to reorganize actin filaments. Here, we provide evidence that Swiprosin-1, a newly identified actin-binding protein, modulates lamellipodial dynamics by regulating the accessibility of F-actin to cofilin. Overexpression of Swiprosin-1 increased lamellipodia formation in B16F10 melanoma cells, whereas knockdown of Swiprosin-1 inhibited EGF-induced lamellipodia formation, and led to a loss of actin stress fibers at the leading edges of cells but not in the cell cortex. Swiprosin-1 strongly facilitated the formation of entangled or clustered F-actin, which remodeled the structural organization of actin filaments making them inaccessible to cofilin. EGF-induced phosphorylation of Swiprosin-1 at Ser183, a phosphorylation site newly identified using mass spectrometry, effectively inhibited clustering of actin filaments and permitted cofilin access to F-actin, resulting in actin depolymerization. Cells overexpressing a Swiprosin-1 phosphorylation-mimicking mutant or a phosphorylation-deficient mutant exhibited irregular membrane dynamics during the protrusion and retraction cycles of lamellipodia. Taken together, these findings suggest that dynamic exchange of Swiprosin-1 phosphorylation and dephosphorylation is a novel mechanism that regulates actin dynamics by modulating the pattern of cofilin activity at the leading edges of cells. 相似文献
2.
Meyer G Kim B van Golen C Feldman EL 《Cellular and molecular life sciences : CMLS》2005,62(4):461-470
Insulin-like growth factor I (IGF-I) is a potent stimulator of neuroblastoma cell motility. Cell motility requires lamellipodium extension at the leading edge of the cell through organized actin polymerization, and IGF-I stimulates lamellipodial elaboration in human neuroblastoma cells. Rac is a Rho GTPase that stimulates lamellipodial formation via the regulation of actin polymerization. In this study, we show that IGF-I-stimulated phosphatidylinositol 3-kinase (PI-3K) activity promotes rac activation and subsequent activation of the down- stream effectors LIM kinase and cofilin. Overexpression of wild-type LIM kinase and wild-type Xenopus ADF/cofilin (XAC) suppresses IGF-I-stimulated motility in SH-SY5Y cells, while expression of dominant negative LIM kinase and constitutively active XAC increases SH-SY5Y motility in the absence of IGF-I stimulation. These results suggest that regulation by cofilin of actin depolymerization is important in the process of neuroblastoma cell motility, and IGF-I regulates cofilin activity in part through PI-3K, rac, and LIM kinase.Received 18 October 2004; received after revision 3 December 2004; accepted 16 December 2004 相似文献
3.
Eoin E. Kelly Conor P. Horgan Mary W. McCaffrey Paul Young 《Cellular and molecular life sciences : CMLS》2011,68(2):185-194
Long-term potentiation (LTP) defines persistent increases in neurotransmission strength at synapses that are triggered by
specific patterns of neuronal activity. LTP, the most widely accepted molecular model for learning, is best characterised
at glutamatergic synapses on dendritic spines. In this context, LTP involves increases in dendritic spine size and the insertion
of glutamate receptors into the post-synaptic spine membrane, which together boost post-synaptic responsiveness to neurotransmitters.
In dendrites, the material required for LTP is sourced from an organelle termed the endosomal-recycling compartment (ERC),
which is localised to the base of dendritic spines. When LTP is induced, material derived from the recycling compartment,
which contains α-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptors (AMPARs), is mobilised into dendritic
spines feeding the increased need for receptors and membrane at the spine neck and head. In this review, we discuss the importance
of endosomal-recycling and the role of key proteins which control these processes in the context of LTP. 相似文献
4.
5.
Rafael Andrés Posada-Duque Omar Ramirez Steffen Härtel Nibaldo C. Inestrosa Felipe Bodaleo Christian González-Billault Alfredo Kirkwood Gloria Patricia Cardona-Gómez 《Cellular and molecular life sciences : CMLS》2017,74(1):153-172
CDK5 is a serine/threonine kinase that is involved in the normal function of the adult brain and plays a role in neurotransmission and synaptic plasticity. However, its over-regulation has been associated with Tau hyperphosphorylation and cognitive deficits. Our previous studies have demonstrated that CDK5 targeting using shRNA-miR provides neuroprotection and prevents cognitive deficits. Dendritic spine morphogenesis and forms of long-term synaptic plasticity—such as long-term potentiation (LTP)—have been proposed as essential processes of neuroplasticity. However, whether CDK5 participates in these processes remains controversial and depends on the experimental model. Using wild-type mice that received injections of CDK5 shRNA-miR in CA1 showed an increased LTP and recovered the PPF in deficient LTP of APPswe/PS1Δ9 transgenic mice. On mature hippocampal neurons CDK5, shRNA-miR for 12 days induced increased dendritic protrusion morphogenesis, which was dependent on Rac activity. In addition, silencing of CDK5 increased BDNF expression, temporarily increased phosphorylation of CaMKII, ERK, and CREB; and facilitated calcium signaling in neurites. Together, our data suggest that CDK5 downregulation induces synaptic plasticity in mature neurons involving Ca2+ signaling and BDNF/CREB activation. 相似文献
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7.
The nervous system is populated by diverse types of neurons, each of which has dendritic trees with strikingly different morphologies. These neuron-specific morphologies determine how dendritic trees integrate thousands of synaptic inputs to generate different firing properties. To ensure proper neuronal function and connectivity, it is necessary that dendrite patterns are precisely controlled and coordinated with synaptic activity. Here, we summarize the molecular and cellular mechanisms that regulate the formation of cell type-specific dendrite patterns during development. We focus on different aspects of vertebrate dendrite patterning that are particularly important in determining the neuronal function; such as the shape, branching, orientation and size of the arbors as well as the development of dendritic spine protrusions that receive excitatory inputs and compartmentalize postsynaptic responses. Additionally, we briefly comment on the implications of aberrant dendritic morphology for nervous system disease. 相似文献
8.
Michael J. Schell 《Cellular and molecular life sciences : CMLS》2010,67(11):1755-1778
The localized control of second messenger levels sculpts dynamic and persistent changes in cell physiology and structure.
Inositol trisphosphate [Ins(1,4,5)P
3] 3-kinases (ITPKs) phosphorylate the intracellular second messenger Ins(1,4,5)P
3. These enzymes terminate the signal to release Ca2+ from the endoplasmic reticulum and produce the messenger inositol tetrakisphosphate [Ins(1,3,4,5)P
4]. Independent of their enzymatic activity, ITPKs regulate the microstructure of the actin cytoskeleton. The immune phenotypes
of ITPK knockout mice raise new questions about how ITPKs control inositol phosphate lifetimes within spatial and temporal
domains during lymphocyte maturation. The intense concentration of ITPK on actin inside the dendritic spines of pyramidal
neurons suggests a role in signal integration and structural plasticity in the dendrite, and mice lacking neuronal ITPK exhibit
memory deficits. Thus, the molecular and anatomical features of ITPKs allow them to regulate the spatiotemporal properties
of intracellular signals, leading to the formation of persistent molecular memories. 相似文献
9.
The primary cilium is an important sensory organelle present in most mammalian cells. Our current studies aim at examining
intracellular molecules that regulate cilia length and/or cilia function in vitro and ex vivo. For the first time, we show
that intracellular cAMP and cAMP-dependent protein kinase (PKA) regulate both cilia length and function in vascular endothelial
cells. Although calcium-dependent protein kinase modulates cilia length, it does not play a significant role in cilia function.
Cilia length regulation also involves mitogen-activated protein kinase (MAPK), protein phosphatase-1 (PP-1), and cofilin.
Furthermore, cofilin regulates cilia length through actin rearrangement. Overall, our study suggests that the molecular interactions
between cilia function and length can be independent of one another. Although PKA regulates both cilia length and function,
changes in cilia length by MAPK, PP-1, or cofilin do not have a direct correlation to changes in cilia function. We propose
that cilia length and function are regulated by distinct, yet complex intertwined signaling pathways. 相似文献
10.
J P Dadonne V Meininger 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1975,280(23):2669-2672
Scanning transmission electron microscopy of the dendritic spines of multipolar neurons in the cat inferior Colliculus was achieved on Golgi semi-thin sections. The three basic types of dendritic spines (ST, MS, TH) were identified. Scanning transmission electron microscopy provides a reliable method for a three dimensional view of these structures at high resolution and consequently a more accurate appreciation of their size. In addition, it could prove very useful in the quantitative analysis of the dendritic spines. 相似文献
11.
Jiong-Yu Hu Zhi-Gang Chu Jian Han Yong-ming Dang Hong Yan Qiong Zhang Guang-ping Liang Yue-Sheng Huang 《Cellular and molecular life sciences : CMLS》2010,67(2):321-333
In both cardiomyocytes and HeLa cells, hypoxia (1% O2) quickly leads to microtubule disruption, but little is known about how microtubule dynamics change during the early stages
of hypoxia. We demonstrate that microtubule associated protein 4 (MAP4) phosphorylation increases while oncoprotein 18/stathmin
(Op18) phosphorylation decreases after hypoxia, but their protein levels do not change. p38/MAPK activity increases quickly
after hypoxia concomitant with MAP4 phosphorylation, and the activated p38/MAPK signaling leads to MAP4 phosphorylation and
to Op18 dephosphorylation, both of which induce microtubule disruption. We confirmed the interaction between phospho-p38 and
MAP4 using immunoprecipitation and found that SB203580, a p38/MAPK inhibitor, increases and MKK6(Glu) overexpression decreases
hypoxic cell viability. Our results demonstrate that hypoxia induces microtubule depolymerization and decreased cell viability
via the activation of the p38/MAPK signaling pathway and changes the phosphorylation levels of its downstream effectors, MAP4
and Op18. 相似文献
12.
Adducin: structure, function and regulation 总被引:7,自引:0,他引:7
Adducin is a ubiquitously expressed membrane-skeletal protein localized at spectrin-actin junctions that binds calmodulin and is an in vivo substrate for protein kinase C (PKC) and Rho-associated kinase. Adducin is a tetramer comprised of either alpha/beta or alpha/gamma heterodimers. Adducin subunits are related in sequence and all contain an N-terminal globular head domain, a neck domain and a C-terminal protease-sensitive tail domain. The tail domains of all adducin subunits end with a highly conserved 22-residue myristoylated alanine-rich C kinase substrate (MARCKS)-related domain that has homology to MARCKS protein. Adducin caps the fast-growing ends of actin filaments and also preferentially recruits spectrin to the ends of filaments. Both the neck and the MARCKS-related domains are required for these activities. The neck domain self-associates to form oligomers. The MARCKS-related domain binds calmodulin and contains the major phosphorylation site for PKC. Calmodulin, gelsolin and phosphorylation by the kinase inhibit in vitro activities of adducin involving actin and spectrin. Recent observations suggest a role for adducin in cell motility, and as a target for regulation by Rho-dependent and Ca2+-dependent pathways. Prominent physiological sites of regulation of adducin include dendritic spines of hippocampal neurons, platelets and growth cones of axons. 相似文献
13.
R.C. May 《Cellular and molecular life sciences : CMLS》2001,58(11):1607-1626
In recent years the Arp2/3 complex has emerged as a central regulator of actin dynamics, assembling and cross-linking actin
filaments to produce a diverse array of cellular structures. Here I discuss our current state of knowledge about this actin-remodelling
machine. The predicted structure of the Arp2/3 complex can be directly correlated with its ability to nucleate, cap and cross-link
actin filaments. A growing family of Arp2/3 complex activators such as the WASP family, type I myosins, and the newly identified
activators cortactin and Abp1p tightly regulate this activity within the cell. Localised activation of the Arp2/3 complex
produces structures such as lamellipodia or actin patches via a process termed dendritic nucleation. Furthermore, several
pathogenic microorganisms have evolved strategies to 'hijack' the Arp2/3 complex to their own advantage. Finally, I discuss
some of the questions which remain unanswered about this fascinating complex.
Received 2 April 2001; received after revision 15 May 2001; accepted 18 May 2001 相似文献
14.
Pyramidal neurons have a complex dendritic arbor containing tens of thousands of synapses. In order for the somatic/axonal
membrane potential to reach action potential threshold, concurrent activation of multiple excitatory synapses is required.
Frequently, instead of a simple algebraic summation of synaptic potentials in the soma, different dendritic compartments contribute
to the integration of multiple inputs, thus endowing the neuron with a powerful computational ability. Most pyramidal neurons
share common functional properties. However, different and sometimes contrasting dendritic integration rules are also observed.
In this review, we focus on the dendritic integration of two neighboring pyramidal neurons in the hippocampus: the well-characterized
CA1 and the much less understood CA2. The available data reveal that the dendritic integration of these neurons is markedly
different even though they are targeted by common inputs at similar locations along their dendrites. This contrasting dendritic
integration results in different routing of information flow and generates different corticohippocampal loops. 相似文献
15.
The synapsins: beyond the regulation of neurotransmitter release 总被引:12,自引:0,他引:12
The synapsins are a family of five closely related neuron-specific phosphoproteins associated with the membranes of synaptic
vesicles. The synapsins have been implicated in the regulation of neurotransmitter release. They tether synaptic vesicles
to actin filaments in a phosphorylation-dependent manner, controlling the number of vesicles available for release at the
nerve terminus. A growing body of evidence suggests that the synapsins play a broad role during neuronal development. They
participate in the formation and maintenance of synaptic contacts among central neurons. In addition, each synapsin has a
specific role during the elongation of undifferentiated processes and their posterior differentiation into axons and dendrites.
In this review, we focus on these novel roles of synapsins during the early stages of development.
Received 26 September 2001; received after revision 8 November 2001; accepted 9 November 2001 相似文献
16.
17.
He L Zhang Z Yu Y Ahmed S Cheung NS Qi RZ 《Cellular and molecular life sciences : CMLS》2011,68(9):1633-1643
The neuronal Cdk5 activator p35 is involved in a multitude of neuronal activities, including cytoskeletal organization. We
show here that p35 directly interacts with filamentous actin (F-actin) but not with monomeric actin (G-actin). Through binding,
p35 induces the formation of actin bundles and stabilizes F-actin against dilution-induced depolymerization. p35 forms intermolecular
self-associations, suggesting that p35 cross-links actin filaments into bundles via its intermolecular self-association. p35
dimerization and association with F-actin occur at the N-terminal region that is absent in the calpain-cleaved product p25,
indicating that such p35 properties are lost by its truncation induced under neurotoxic conditions. Using p35 phosphorylated
by Cdk5 and a mutational approach, we demonstrate that the phosphorylation of p35 promotes its homodimerization and p35-induced
formation of F-actin bundles. In addition, the phosphorylation regulates p35 distribution to microtubule and actin cytoskeletons.
Together, these observations define a novel function for p35 in cytoskeletal regulation. 相似文献
18.
Neurotrophins and neuronal differentiation in the central nervous system 总被引:10,自引:0,他引:10
McAllister AK 《Cellular and molecular life sciences : CMLS》2001,58(8):1054-1060
The central nervous system requires the proper formation of exquisitely precise circuits to function properly. These neuronal
circuits are assembled during development by the formation of synaptic connections between hundreds of thousands of differentiating
neurons. For these circuits to form correctly, neurons must elaborate precisely patterned axonal and dendritic arbors. Although
the cellular and molecular mechanisms that guide neuronal differentiation and formation of connections remain mostly unknown,
the neurotrophins have emerged recently as attractive candidates for regulating neuronal differentiation in the developing
brain. The experiments reviewed here provide strong support for a bifunctional role for the neurotrophins in axonal and dendritic
growth and are consistent with the exciting possibility that the neurotrophins might mediate activity-dependent synaptic plasticity. 相似文献
19.
Massicotte G 《Cellular and molecular life sciences : CMLS》2000,57(11):1542-1550
Long-term potentiation (LTP) and long-term depression (LTD) are two electrophysiological models that have been studied extensively in recent years as they may represent basic mechanisms in many neuronal networks to store certain types of information. In several brain regions, it has been shown that these two forms of synaptic plasticity require sufficient dendritic depolarization, with the amplitude of the calcium signal being crucial for the generation of either LTP or LTD. The rise in calcium concentration mediated by the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to stimulate various calcium-dependent enzymatic processes that could convert the induction signal into long-lasting changes in synaptic structure; protein kinases and phosphatases have so far been considered predominantly with regard to LTP and LTD formation. According to several lines of experimental evidence, changes in synaptic function observed with LTP and LTD are thought to be the result of modifications of postsynaptic currents mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors. Moreover, it has become apparent recently that activation of the calcium-dependent enzyme phospholipase A2 (PLA2) could be part of the molecular mechanisms involved in alterations of AMPA receptor properties during long-term changes in synaptic operation. In the present review, we will first describe the results that indicate a critical role of the phospholipases in regulating synaptic function. Next, sections will be devoted to the effects of PLA2 and phospholipids on the binding properties of glutamate receptors, and a revised biochemical model will be presented as an attempt to integrate the PLA2 enzyme into the mechanisms ( in particular kinases and phosphatases) that participate in adaptive neural plasticity. Finally, we will review data relevant to the issue of selective changes in AMPA binding after environmental enrichment and LTP. 相似文献
20.
The development of neuronal connectivity requires the growth of axons to their target region and the formation of dendritic
trees that extend into specific layers. Within the target region growth cones, the tips of extending axons are guided to finer
target fields including specific subcellular compartments where they form synapses. In this article we highlight recent progress
on molecular aspects of axonal subcellular target selection such as the axon initial segment or specific sublaminae of the
vertebrate retina. We then discuss the very recent progress on the molecular analysis of synapse formation in the central
nervous system, including the direction of differentiation into an inhibitory or excitatory synapse. Apparently, initial synaptic
contacts are structurally and functionally modulated by neuronal activity, raising the question how neuronal activity can
modify synaptic circuits. We therefore also focus on neural proteins that are up-regulated, secreted or converted by synaptic
activity and, thus, might represent molecular candidates for experience-driven refinement or remodeling of synaptic connections.
Received 5 July 2005; received after revision 19 August 2005; accepted 2 September 2005 相似文献