Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis

Hotulainen, Pirta; Llano, Olaya; Smirnov, Sergei; Tanhuanpää, Kimmo; Faix, Jan; Rivera, Claudio; Lappalainen, Pekka

doi:10.1083/jcb.200809046

Cited by 323 publications

(417 citation statements)

References 60 publications

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“…Depletion of mDia2 in cultured neurons resulted in shorter dendritic protrusions whereas overexpression of active mDia2 led to long dendritic filopodia 80 . In addition to the regulation of spine morphogenesis, mDia2/DFR3 has a significant role in neurite extension 81 .…”

Section: Accepted Manuscriptmentioning

confidence: 93%

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Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Section: Accepted Manuscriptmentioning

confidence: 93%

“…The formin family of proteins are known to polymerize straight, non-branched actin filaments 79 ( Figure 1). The small GTPase Rif, and its downstream effector mDia2, play a central role in regulating actin dynamics during dendritic filopodia elongation 80 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Previous studies have established roles of the small GTPase Rif and its effector mDia2, Arp2/3 and ADF/cofilin in the processes of filopodia elongation, spine head expansion and maintenance of spine length and morphology, respectively [8]. However, our understanding of regulatory mechanisms underlying actin-dependent spine maturation and dynamics is still incomplete.…”

Section: Introductionmentioning

confidence: 99%

Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap

et al. 2015

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Dendritic spines are actin-rich membrane protrusions that are the major sites of excitatory synaptic input in the mammalian brain, and their morphological plasticity provides structural basis for learning and memory. Here we report that endophilin A1, with a well-established role in clathrin-mediated synaptic vesicle endocytosis at the presynaptic terminal, also localizes to dendritic spines and is required for spine morphogenesis, synapse formation and synaptic function. We identify p140Cap, a regulator of cytoskeleton reorganization, as a downstream effector of endophilin A1 and demonstrate that disruption of their interaction impairs spine formation and maturation. Moreover, we demonstrate that knockdown of endophilin A1 or p140Cap impairs spine stabilization and synaptic function. We further show that endophilin A1 regulates the distribution of p140Cap and its downstream effector, the F-actin-binding protein cortactin as well as F-actin enrichment in dendritic spines. Together, these results reveal a novel function of postsynaptic endophilin A1 in spine morphogenesis, stabilization and synaptic function through the regulation of p140Cap.

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“…They lack the rounded spine head and are thought to serve as the first contact sites between nascent axonal boutons and dendrites during the development of the synapse. Much (although not all) of the F-actin within dendritic filopodia is unbranched (6), and studies knocking down the formin mDia2 demonstrate that it is important for the actindependent emergence of filopodia during this initial stage of spine formation (19). The formin FMN2 may also be important for either spine formation or maintenance.…”

Section: Dendritic Spine Actin Regulatorsmentioning

confidence: 99%

Actin Out: Regulation of the Synaptic Cytoskeleton

Spence

Soderling

2015

Journal of Biological Chemistry

153

122

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The small size of dendritic spines belies the elaborate role they play in excitatory synaptic transmission and ultimately complex behaviors. The cytoskeletal architecture of the spine is predominately composed of actin filaments. These filaments, which at first glance might appear simple, are also surprisingly complex. They dynamically assemble into different structures and serve as a platform for orchestrating the elaborate responses of the spine during spinogenesis and experience-dependent plasticity. Multiple mutations associated with human neurodevelopmental and psychiatric disorders involve genes that encode regulators of the synaptic cytoskeleton. A major, unresolved question is how the disruption of specific actin filament structures leads to the onset and progression of complex synaptic and behavioral phenotypes. This review will cover established and emerging mechanisms of actin cytoskeletal remodeling and how this influences specific aspects of spine biology that are implicated in disease.Dendritic spines are morphologically diverse, actin-rich protrusions emerging from dendritic shafts that serve as the receiving sites for the majority of excitatory synaptic transmission in the brain. First described over a century ago by Ramón y Cajal, dendritic spines typically consist of a spine head, which can range in size from 0.5 to 2 m in length, and thin spine neck (ϳ0.2 m thick) (Fig. 1). Their essential function is to compartmentalize biochemical and electrical signals in response to synaptic activation (1). Dendritic spines are supported by an underlying cytoskeleton that is almost exclusively composed of actin filaments, which can be up to ϳ200 nm long (2). Remodeling of this densely packed actin governs most, if not all, dendritic spine physiology. This includes spine formation and maintenance, synaptic adhesion, receptor endocytosis and exocytosis, and synaptic plasticity (Fig. 1). Further, the actin cytoskeleton drives dendritic spine turnover and morphological changes that occur in vivo in response to experience (3). Finally, aberrations in dendritic spine morphology and density are linked to a variety of neurological disorders such as schizophrenia (SZ) 2 and intellectual disability (ID) (4). Recent studies link de novo mutations associated with increased risk of complex psychiatric disorders such as SZ to genes encoding regulators of the post-synaptic actin cytoskeleton (5) (see Fig. 3). Together these findings strongly imply that proper maintenance of the spine actin cytoskeleton is critical for spine functionality and neuronal connectivity. This review will focus on the nuts and bolts of actin dynamics in spines as well as recent developments in the modulation of the synaptic cytoskeleton in two crucial dendritic spine processes whose disturbances are linked with synapse pathologies: synaptic adhesion and synaptic plasticity.

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Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis

Cited by 323 publications

References 60 publications

Dendritic spine actin cytoskeleton in autism spectrum disorder

Dendritic spine actin cytoskeleton in autism spectrum disorder

Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap

Actin Out: Regulation of the Synaptic Cytoskeleton

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