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

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.

Download Full-text

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

Biological Chemistry ◽

10.1515/hsz-2019-0110 ◽

2019 ◽

Vol 400 (9) ◽

pp. 1129-1139 ◽

Cited By ~ 2

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.

Download Full-text

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

The Journal of Cell Biology ◽

10.1083/jcb.151.1.53 ◽

2000 ◽

Vol 151 (1) ◽

pp. 53-68 ◽

Cited By ~ 78

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.

Download Full-text

Caldendrin and myosin V regulate synaptic spine apparatus localization via ER stabilization in dendritic spines

The EMBO Journal ◽

10.15252/embj.2020106523 ◽

2021 ◽

Author(s):

Anja Konietzny ◽

Jasper Grendel ◽

Alan Kadek ◽

Michael Bucher ◽

Yuhao Han ◽

...

Keyword(s):

Dendritic Spines ◽

Myosin V ◽

Spine Apparatus

Download Full-text

Endoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses

Nature Communications ◽

10.1038/s41467-020-18889-5 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Alberto Perez-Alvarez ◽

Shuting Yin ◽

Christian Schulze ◽

John A. Hammer ◽

Wolfgang Wagner ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Dendritic Spines ◽

Low Frequency ◽

Pyramidal Cells ◽

Long Term Potentiation ◽

Dominant Negative ◽

Synaptic Activity ◽

Small Subset ◽

Myosin V

Abstract In hippocampal pyramidal cells, a small subset of dendritic spines contain endoplasmic reticulum (ER). In large spines, ER frequently forms a spine apparatus, while smaller spines contain just a single tubule of smooth ER. Here we show that the ER visits dendritic spines in a non-random manner, targeting spines during periods of high synaptic activity. When we blocked ER motility using a dominant negative approach against myosin V, spine synapses became stronger compared to controls. We were not able to further potentiate these maxed-out synapses, but long-term depression (LTD) was readily induced by low-frequency stimulation. We conclude that the brief ER visits to active spines have the important function of preventing runaway potentiation of individual spine synapses, keeping most of them at an intermediate strength level from which both long-term potentiation (LTP) and LTD are possible.

Download Full-text

Endoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses

10.1101/2020.07.30.228155 ◽

2020 ◽

Cited By ~ 1

Author(s):

Alberto Perez-Alvarez ◽

Shuting Yin ◽

Christian Schulze ◽

John A. Hammer ◽

Wolfgang Wagner ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Dendritic Spines ◽

Low Frequency ◽

Pyramidal Cells ◽

Dominant Negative ◽

Synaptic Activity ◽

Small Subset ◽

Myosin V ◽

Highly Active ◽

Frequency Stimulation

AbstractIn hippocampal pyramidal cells, a small subset of dendritic spines contain endoplasmic reticulum (ER). In large spines, ER frequently forms a spine apparatus, while smaller spines contain just a single tubule of smooth ER. Here we show that the ER visits dendritic spines in a non-random manner, targeting spines during periods of high synaptic activity. When we blocked ER motility using a dominant negative approach against myosin V, spine synapses became stronger compared to controls. We were not able to further potentiate these maxed-out synapses, but LTD was readily induced by low-frequency stimulation. We conclude that the brief ER visits to active spines have the important function of preventing runaway potentiation of individual spine synapses, keeping most of them at an intermediate strength level from which both LTP and LTD are possible.

Download Full-text

Characterization of neuronal synaptopodin reveals a myosin V-dependent mechanism of synaptopodin clustering at the post-synaptic sites

10.1101/526509 ◽

2019 ◽

Cited By ~ 3

Author(s):

Judit Gonzalez-Gallego ◽

Anja Konietzny ◽

Alberto Perez-Alvarez ◽

Julia Baer ◽

Urban Maier ◽

...

Keyword(s):

Dendritic Spines ◽

Pyramidal Neurons ◽

Super Resolution ◽

Myosin V ◽

Interaction Partners ◽

Spine Apparatus ◽

Tight Association ◽

Super Resolution Microscopy ◽

Dependent Mechanism

The spine apparatus (SA) is an endoplasmic reticulum-related organelle which is present in a subset of dendritic spines in cortical and pyramidal neurons. The synaptopodin protein localizes between the stacks of the spine apparatus and is essential for the formation of this unique organelle. Although several studies have demonstrated the significance of the SA and synaptopodin in calcium homeostasis and plasticity of dendritic spines, it is still unclear what factors contribute to its stability at the synapse and whether the SA is locally formed or it is actively delivered to the spines. In this study we show that synaptopodin clusters are stable at their locations. We found no evidence of active microtubule-based transport for synaptopodin. Instead new clusters were emerging in the spines, which we interpret as the SA being assembled on-site. Furthermore, using super-resolution microscopy we show a tight association of synaptopodin with actin filaments. We identify the actin-based motor proteins myosin V and VI as novel interaction partners of synaptopodin and demonstrate that myosin V is important for the formation and/or maintenance of the SA.

Download Full-text

Synaptic organization of the gustatory NST

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100168487 ◽

1994 ◽

Vol 52 ◽

pp. 150-151

Author(s):

M. C. Whitehead

Keyword(s):

Central Nervous System ◽

Dendritic Spines ◽

Fundamental Problem ◽

Cell Types ◽

Brain Regions ◽

Excitatory Synapses ◽

Solitary Tract ◽

Synaptic Organization ◽

Synaptic Junctions ◽

Afferent Terminals

A fundamental problem in taste research is to determine how gustatory signals are processed and disseminated in the mammalian central nervous system. An important first step toward understanding information processing is the identification of cell types in the nucleus of the solitary tract (NST) and their synaptic relationships with oral primary afferent terminals. Facial and glossopharyngeal (LIX) terminals in the hamster were labelled with HRP, examined with EM, and characterized as containing moderate concentrations of medium-sized round vesicles, and engaging in asymmetrical synaptic junctions. Ultrastructurally the endings resemble excitatory synapses in other brain regions.Labelled facial afferent endings in the RC subdivision synapse almost exclusively with distal dendrites and dendritic spines of NST cells. Most synaptic relationships between the facial synapses and the dendrites are simple. However, 40% of facial endings engage in complex synaptic relationships within glomeruli containing unlabelled axon endings particularly ones termed "SP" endings. SP endings are densely packed with small, pleomorphic vesicles and synapse with both the facial endings and their postsynaptic dendrites by means of nearly symmetrical junctions.

Download Full-text

Three-dimensional structure of dendritic spines, neuronal specializations that impart both stability and flexibility to synaptic function

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100146308 ◽

1993 ◽

Vol 51 ◽

pp. 92-93

Author(s):

Kristen M. Harris

Keyword(s):

Dendritic Spines ◽

Three Dimensional ◽

Synaptic Function ◽

Dimensional Structure ◽

Excitatory Synapses ◽

Concept Of Function ◽

Section Electron ◽

High Quality Information ◽

The Central Nervous System ◽

Mathematical Analyses

Dendritic spines are the tiny protrusions that stud the surface of many neurons and they are the location of over 90% of all excitatory synapses that occur in the central nervous system. Their small size and variable shapes has in large part made detailed study of their structure refractory to conventional light microscopy and single section electron microscopy (EM). Yet their widespread occurrence and likely involvement in learning and memory has motivated extensive efforts to obtain quantitative descriptions of spines in both steady state and dynamic conditions. Since the seminal mathematical analyses of D’Arcy Thompson, the power of establishing quantitatively key parameters of structure has become recognized as a foundation of successful biological inquiry. For dendritic spines highly precise determinations of structure and its variation are proving themselves as the kingpin for establishing a valid concept of function. The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has produced a flurry of new considerations of their role in synaptic transmission.

Download Full-text