scholarly journals Synbindin, a Novel Syndecan-2–Binding Protein in Neuronal Dendritic Spines

2000 ◽  
Vol 151 (1) ◽  
pp. 53-68 ◽  
Author(s):  
Iryna M. Ethell ◽  
Kazuki Hagihara ◽  
Yoshiaki Miura ◽  
Fumitoshi Irie ◽  
Yu Yamaguchi
Keyword(s):  
Dendritic Spines ◽  
Membrane Trafficking ◽  
Hippocampal Neurons ◽  
Critical Role ◽  
Postsynaptic Membrane ◽  
Synaptic Membrane ◽  
Excitatory Synapses ◽  
Spine Formation ◽  
Intracellular Vesicles ◽  
Spine Morphogenesis

Dendritic spines are small protrusions on the surface of dendrites that receive the vast majority of excitatory synapses. We previously showed that the cell-surface heparan sulfate proteoglycan syndecan-2 induces spine formation upon transfection into hippocampal neurons. This effect requires the COOH-terminal EFYA sequence of syndecan-2, suggesting that cytoplasmic molecules interacting with this sequence play a critical role in spine morphogenesis. Here, we report a novel protein that binds to the EFYA motif of syndecan-2. This protein, named synbindin, is expressed by neurons in a pattern similar to that of syndecan-2, and colocalizes with syndecan-2 in the spines of cultured hippocampal neurons. In transfected hippocampal neurons, synbindin undergoes syndecan-2–dependent clustering. Synbindin is structurally related to yeast proteins known to be involved in vesicle transport. Immunoelectron microscopy localized synbindin on postsynaptic membranes and intracellular vesicles within dendrites, suggesting a role in postsynaptic membrane trafficking. Synbindin coimmunoprecipitates with syndecan-2 from synaptic membrane fractions. Our results show that synbindin is a physiological syndecan-2 ligand on dendritic spines. We suggest that syndecan-2 induces spine formation by recruiting intracellular vesicles toward postsynaptic sites through the interaction with synbindin.

scholarly journals Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

2019 ◽  
Vol 400 (9) ◽  
pp. 1129-1139 ◽  
Author(s):  
Iryna Hlushchenko ◽  
Pirta Hotulainen
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Signal Molecule ◽  
Brain Functions ◽  
Dendritic Shaft ◽  
Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

scholarly journals Synaptic anchoring of the endoplasmic reticulum depends on myosin V and caldendrin activity

2020 ◽  
Author(s):  
Anja Konietzny ◽  
Jasper Grendel ◽  
Nathalie Hertrich ◽  
Dick H. W. Dekkers ◽  
Jeroen A. A. Demmers ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Motor Function ◽  
Light Chain ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Molecular Diversity ◽  
Fine Tuning ◽  
Excitatory Synapses ◽  
Myosin V ◽  
Spine Apparatus

AbstractExcitatory synapses of principal hippocampal neurons are frequently located on dendritic spines. The dynamic strengthening or weakening of individual inputs results in a great structural and molecular diversity of dendritic spines. Active spines with large Ca2+ transients are frequently invaded by a single protrusion from the endoplasmic reticulum (ER), which is dynamically transported into and out of spines by the actin-based motor myosin V. An increase in synaptic strength often correlates with stable anchoring of the ER, followed by the formation of the spine apparatus organelle. Here we show that synaptic ER stabilization depends on the interplay of two Ca2+-binding proteins: calmodulin serves as a light chain of myosin V and activates the motor function, whereas caldendrin acts as an inhibitor which transforms myosin into a stationary F-actin tether. Together, they provide a Ca2+-sensing module for fine-tuning myosin V activity and thereby regulate the formation of the spine apparatus in a subset of active dendritic spines.

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 Native KCC2 interactome reveals PACSIN1 as a critical regulator of synaptic inhibition

2017 ◽  
Author(s):  
Vivek Mahadevan ◽  
C. Sahara Khademullah ◽  
Zahra Dargaei ◽  
Jonah Chevrier ◽  
Pavel Uvarov ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Neurological Disorders ◽  
Hippocampal Neurons ◽  
Regulatory Protein ◽  
Reversal Potential ◽  
Negative Regulator ◽  
Excitatory Synapses ◽  
Receptor Recycling ◽  
Spine Morphogenesis ◽  
Potent Negative Regulator

AbstractKCC2 is a neuron-specific K+-Cl− cotransporter essential for establishing the Cl− gradient required for hyperpolarizing inhibition. KCC2 is highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes to numerous human neurological disorders including epilepsy and neuropathic pain. Using unbiased functional proteomics, we identified the KCC2-interactome in the mouse brain to determine KCC2-protein interactions that regulate KCC2 function. Our analysis revealed that KCC2 interacts with a diverse set of proteins, and its most predominant interactors play important roles in postsynaptic receptor recycling. The most abundant KCC2 interactor is a neuronal endocytic regulatory protein termed PACSIN1 (SYNDAPIN1). We verified the PACSIN1-KCC2 interaction biochemically and demonstrated that shRNA knockdown of PACSIN1 in hippocampal neurons significantly increases KCC2 expression and hyperpolarizes the reversal potential for Cl−. Overall, our global native-KCC2 interactome and subsequent characterization revealed PACSIN1 as a novel and potent negative regulator of KCC2.

scholarly journals The septin cytoskeleton facilitates membrane retraction during motility and blebbing

2012 ◽  
Vol 196 (1) ◽  
pp. 103-114 ◽  
Author(s):  
Julia K. Gilden ◽  
Sebastian Peck ◽  
Yi-Chun M. Chen ◽  
Matthew F. Krummel
Keyword(s):  
Plasma Membrane ◽  
Dendritic Spines ◽  
Membrane Trafficking ◽  
Shape Change ◽  
Critical Role ◽  
Regulatory Volume Decrease ◽  
Physiological Processes ◽  
Amoeboid Motility ◽  
Dynamic Shape ◽  
Volume Decrease

Increasing evidence supports a critical role for the septin cytoskeleton at the plasma membrane during physiological processes including motility, formation of dendritic spines or cilia, and phagocytosis. We sought to determine how septins regulate the plasma membrane, focusing on this cytoskeletal element’s role during effective amoeboid motility. Surprisingly, septins play a reactive rather than proactive role, as demonstrated during the response to increasing hydrostatic pressure and subsequent regulatory volume decrease. In these settings, septins were required for rapid cortical contraction, and SEPT6-GFP was recruited into filaments and circular patches during global cortical contraction and also specifically during actin filament depletion. Recruitment of septins was also evident during excessive blebbing initiated by blocking membrane trafficking with a dynamin inhibitor, providing further evidence that septins are recruited to facilitate retraction of membranes during dynamic shape change. This function of septins in assembling on an unstable cortex and retracting aberrantly protruding membranes explains the excessive blebbing and protrusion observed in septin-deficient T 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 Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Junjun Zhao ◽  
Albert Hiu Ka Fok ◽  
Ruolin Fan ◽  
Pui-Yi Kwan ◽  
Hei-Lok Chan ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Gene Duplication ◽  
Hippocampal Neurons ◽  
Motor Proteins ◽  
Arginine Methylation ◽  
Memory Formation ◽  
Conditional Knockout ◽  
Excitatory Synapses ◽  
Functional Specificity ◽  
Spine Morphogenesis

The kinesin I family of motor proteins are crucial for axonal transport, but their roles in dendritic transport and postsynaptic function are not well-defined. Gene duplication and subsequent diversification give rise to three homologous kinesin I proteins (KIF5A, KIF5B and KIF5C) in vertebrates, but it is not clear whether and how they exhibit functional specificity. Here we show that knockdown of KIF5A or KIF5B differentially affects excitatory synapses and dendritic transport in hippocampal neurons. The functional specificities of the two kinesins are determined by their diverse carboxyl-termini, where arginine methylation occurs in KIF5B and regulates its function. KIF5B conditional knockout mice exhibit deficits in dendritic spine morphogenesis, synaptic plasticity and memory formation. Our findings provide insights into how expansion of the kinesin I family during evolution leads to diversification and specialization of motor proteins in regulating postsynaptic function.

scholarly journals Loss of O-GlcNAcylation on MeCP2 Thr 203 Leads to Neurodevelopmental Disorders

2020 ◽  
Author(s):  
Juanxian Cheng ◽  
Zhe Zhao ◽  
Liping Chen ◽  
Ruijing Du ◽  
Yan Wu ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neural Development ◽  
Hippocampal Neurons ◽  
Critical Role ◽  
Dendrite Development ◽  
Genome Wide ◽  
Mouse Cerebral Cortex ◽  
Functional Regulation ◽  
Spine Morphogenesis

AbstractMutations of the X-linked methyl-CpG-binding protein 2 (MECP2) gene in humans are responsible for most cases of Rett syndrome (RTT), an X-linked progressive neurological disorder. While genome-wide screens in clinical trials reveal several putative RTT-associated mutations on MECP2, their causative relevance regarding the functional regulation of MeCP2 on the etiologic sites at the protein level require more evidence. In this study, we demonstrate that MeCP2 is dynamically modified by O-linked-β-N-acetylglucosamine (O-GlcNAc) at threonine 203 (T203), an etiologic site in RTT patients. Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impairs dendrite development and spine maturation in cultured hippocampal neurons, and disrupts neuronal migration, dendritic spine morphogenesis and dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex. Mechanistically, genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreases neuronal activity-induced induction of Bdnf transcription. Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via BDNF.

scholarly journals Polarization of actin cytoskeleton is reduced in dendritic protrusions during early spine development in hippocampal neuron

2012 ◽  
Vol 23 (16) ◽  
pp. 3167-3177 ◽  
Author(s):  
Vedakumar Tatavarty ◽  
Sulagna Das ◽  
Ji Yu
Keyword(s):  
Actin Cytoskeleton ◽  
Dendritic Spines ◽  
Myosin Ii ◽  
Retrograde Flow ◽  
Actin Remodeling ◽  
Spine Formation ◽  
Spatially Resolved ◽  
Kinetic Rates ◽  
Quantitative Understanding ◽  
Spine Morphogenesis

Dendritic spines are small protrusions that receive synaptic signals in neuronal networks. The actin cytoskeleton plays a key role in regulating spine morphogenesis, as well as in the function of synapses. Here we report the first quantitative measurement of F-actin retrograde flow rate in dendritic filopodia, the precursor of dendritic spines, and in newly formed spines, using a technique based on photoactivation localization microscopy. We found a fast F-actin retrograde flow in the dendritic filopodia but not in the spine necks. The quantification of F-actin flow rates, combined with fluorescence recovery after photobleaching measurements, allowed for a full quantification of spatially resolved kinetic rates of actin turnover, which was not previously feasible. Furthermore we provide evidences that myosin II regulates the actin flow in dendritic filopodia and translocates from the base to the tip of the protrusion upon spine formation. Rac1 inhibition led to mislocalization of myosin II, as well as to disruption of the F-actin flow. These results provide advances in the quantitative understanding of F-actin remodeling during spine formation.

scholarly journals Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus

2003 ◽  
Vol 163 (6) ◽  
pp. 1313-1326 ◽  
Author(s):  
Mark Henkemeyer ◽  
Olga S. Itkis ◽  
Michelle Ngo ◽  
Peter W. Hickmott ◽  
Iryna M. Ethell
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Tyrosine Kinases ◽  
Hippocampal Neurons ◽  
Receptor Tyrosine Kinases ◽  
Triple Mutant ◽  
Spine Formation ◽  
Truncating Mutation ◽  
Ephb Receptor ◽  
Spine Development

Here, using a genetic approach, we dissect the roles of EphB receptor tyrosine kinases in dendritic spine development. Analysis of EphB1, EphB2, and EphB3 double and triple mutant mice lacking these receptors in different combinations indicates that all three, although to varying degrees, are involved in dendritic spine morphogenesis and synapse formation in the hippocampus. Hippocampal neurons lacking EphB expression fail to form dendritic spines in vitro and they develop abnormal spines in vivo. Defective spine formation in the mutants is associated with a drastic reduction in excitatory glutamatergic synapses and the clustering of NMDA and AMPA receptors. We show further that a kinase-defective, truncating mutation in EphB2 also results in abnormal spine development and that ephrin-B2–mediated activation of the EphB receptors accelerates dendritic spine development. These results indicate EphB receptor cell autonomous forward signaling is responsible for dendritic spine formation and synaptic maturation in hippocampal neurons.

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