Dendritic Spine Initiation in Brain Development, Learning and Diseases and Impact of BAR-Domain Proteins

Khanal, Pushpa; Hotulainen, Pirta

doi:10.3390/cells10092392

Cited by 27 publications

(16 citation statements)

References 179 publications

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“…Specifically, its dynamic assembly/disassembly participates in the generation of microdomains; its interaction with specific cytoskeletal and membrane components supports modulation of synaptic functions [ 35 , 41 ]. The density of spiny post-synapse distribution, growing in children, reaches high values in mature humans, when density of inhibitory synapses is lower [ 42 , 43 ]. During their existence, many spines undergo dynamic changes, going from appearing, to enlarging, shrinking, and disappearing.…”

Section: Post-synapses With Spinesmentioning

confidence: 99%

“…During their existence, many spines undergo dynamic changes, going from appearing, to enlarging, shrinking, and disappearing. When dependent on excitatory/inhibitory inputs and experience, their activities are defined extrinsic; when independent of external inputs, they are defined intrinsic [ 43 , 44 ]. Intrinsic dynamics play important roles in memory management and adaptations [ 35 ].…”

Section: Post-synapses With Spinesmentioning

confidence: 99%

“…Confocal microscopy studies have identified the mechanisms by which spines emerge from dendrite fibers and their individual structure is recognized. The mechanisms by which various types of spines initiate their activity are well known [ 35 , 40 , 43 ]. The ensuing processes are highly relevant.…”

Section: Post-synapses With Spinesmentioning

confidence: 99%

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Post-Synapses in the Brain: Role of Dendritic and Spine Structures

Meldolesi

2022

Biomedicines

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Brain synapses are neuronal structures of the greatest interest. For a long time, however, the knowledge about them was variable, and interest was mostly focused on their pre-synaptic portions, especially neurotransmitter release from axon terminals. In the present review interest is focused on post-synapses, the structures receiving and converting pre-synaptic messages. Upon further modulation, such messages are transferred to dendritic fibers. Dendrites are profoundly different from axons; they are shorter and of variable thickness. Their post-synapses are of two types. Those called flat/intended/aspines, integrated into dendritic fibers, are very frequent in inhibitory neurons. The spines, small and stemming protrusions, connected to dendritic fibers by their necks, are present in almost all excitatory neurons. Several structures and functions including the post-synaptic densities and associated proteins, the nanoscale mechanisms of compartmentalization, the cytoskeletons of actin and microtubules, are analogous in the two post-synaptic forms. However other properties, such as plasticity and its functions of learning and memory, are largely distinct. Several properties of spines, including emersion from dendritic fibers, growth, change in shape and decreases in size up to disappearance, are specific. Spinal heads correspond to largely independent signaling compartments. They are motile, their local signaling is fast, however transport through their thin necks is slow. When single spines are activated separately, their dendritic effects are often lacking; when multiple spines are activated concomitantly, their effects take place. Defects of post-synaptic responses, especially those of spines, take place in various brain diseases. Here alterations affecting symptoms and future therapy are shown to occur in neurodegenerative diseases and autism spectrum disorders.

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Section: Post-synapses With Spinesmentioning

confidence: 99%

Section: Post-synapses With Spinesmentioning

confidence: 99%

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Post-Synapses in the Brain: Role of Dendritic and Spine Structures

Meldolesi

2022

Biomedicines

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“…During development, dendritic spines are generally thought to form as thin filopodia-like protrusions that arise from the dendritic shaft and stabilize upon contact with axons ( Marrs et al, 2001 ; Yoshihara et al, 2009 ; Khanal and Hotulainen, 2021 ). These spines subsequently form enlarged heads, containing various postsynaptic components that are connected to the dendrite by a thin neck ( Hotulainen and Hoogenraad, 2010 ; Chidambaram et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Actin capping protein regulates postsynaptic spine development through CPI-motif interactions

Myers

Fan

McConnell

et al. 2022

Front. Mol. Neurosci.

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Dendritic spines are small actin-rich protrusions essential for the formation of functional circuits in the mammalian brain. During development, spines begin as dynamic filopodia-like protrusions that are then replaced by relatively stable spines containing an expanded head. Remodeling of the actin cytoskeleton plays a key role in the formation and modification of spine morphology, however many of the underlying regulatory mechanisms remain unclear. Capping protein (CP) is a major actin regulating protein that caps the barbed ends of actin filaments, and promotes the formation of dense branched actin networks. Knockdown of CP impairs the formation of mature spines, leading to an increase in the number of filopodia-like protrusions and defects in synaptic transmission. Here, we show that CP promotes the stabilization of dendritic protrusions, leading to the formation of stable mature spines. However, the localization and function of CP in dendritic spines requires interactions with proteins containing a capping protein interaction (CPI) motif. We found that the CPI motif-containing protein Twinfilin-1 (Twf1) also localizes to spines where it plays a role in CP spine enrichment. The knockdown of Twf1 leads to an increase in the density of filopodia-like protrusions and a decrease in the stability of dendritic protrusions, similar to CP knockdown. Finally, we show that CP directly interacts with Shank and regulates its spine accumulation. These results suggest that spatiotemporal regulation of CP in spines not only controls the actin dynamics underlying the formation of stable postsynaptic spine structures, but also plays an important role in the assembly of the postsynaptic apparatus underlying synaptic function.

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“…The morphological changes associated with the organization and dynamics of the synaptic actin cytoskeleton regulate activity-dependent synaptic plasticity including the formation of new synapses as well as remodeling of existing connections. This plasticity represents a key mechanism for rewiring neural circuits during development, learning and memory, and in brain disorders (Stuchlik, 2014 ; Khanal and Hotulainen, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Revisiting I-BAR Proteins at Central Synapses

Chatzi

Westbrook

2021

Front. Neural Circuits

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Dendritic spines, the distinctive postsynaptic feature of central nervous system (CNS) excitatory synapses, have been studied extensively as electrical and chemical compartments, as well as scaffolds for receptor cycling and positioning of signaling molecules. The dynamics of the shape, number, and molecular composition of spines, and how they are regulated by neural activity, are critically important in synaptic efficacy, synaptic plasticity, and ultimately learning and memory. Dendritic spines originate as outward protrusions of the cell membrane, but this aspect of spine formation and stabilization has not been a major focus of investigation compared to studies of membrane protrusions in non-neuronal cells. We review here one family of proteins involved in membrane curvature at synapses, the BAR (Bin-Amphiphysin-Rvs) domain proteins. The subfamily of inverse BAR (I-BAR) proteins sense and introduce outward membrane curvature, and serve as bridges between the cell membrane and the cytoskeleton. We focus on three I-BAR domain proteins that are expressed in the central nervous system: Mtss2, MIM, and IRSp53 that promote negative, concave curvature based on their ability to self-associate. Recent studies suggest that each has distinct functions in synapse formation and synaptic plasticity. The action of I-BARs is also shaped by crosstalk with other signaling components, forming signaling platforms that can function in a circuit-dependent manner. We discuss another potentially important feature—the ability of some BAR domain proteins to impact the function of other family members by heterooligomerization. Understanding the spatiotemporal resolution of synaptic I-BAR protein expression and their interactions should provide insights into the interplay between activity-dependent neural plasticity and network rewiring in the CNS.

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Dendritic Spine Initiation in Brain Development, Learning and Diseases and Impact of BAR-Domain Proteins

Cited by 27 publications

References 179 publications

Post-Synapses in the Brain: Role of Dendritic and Spine Structures

Post-Synapses in the Brain: Role of Dendritic and Spine Structures

Actin capping protein regulates postsynaptic spine development through CPI-motif interactions

Revisiting I-BAR Proteins at Central Synapses

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