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Cited by 360Neuroscience and Neuropharmacology ResearchCellular Mechanics and InteractionsAxon Guidance and Neuronal Signaling

Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis

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Hotulainen, Pirta, Llano, Olaya, Smirnov, Sergei, Tanhuanpää, Kimmo, Faix, Jan, Rivera, Claudio, Lappalainen, Pekka·2009·Journal of Cell Biology
DOI 10.1083/jcb.200809046PMC PMC2700375
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Abstract

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.

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  • Cofilin is a highly abundant actin-regulatory protein that binds to and alters the physical properties of F-actin.

    “Cofilin is a highly abundant actin-regulatory protein, which binds to and alters the physical properties of F-actin1314.”

    From State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines (2016) · cites this paper as [14]

    The Introduction says ADF/cofilins sever and depolymerize actin filaments, and the Discussion describes cofilin-1–induced filament disassembly. The Results report high cofilin-1 levels in the dendritic shaft, but do not establish that cofilin is highly abundant in general or specifically describe its binding to F-actin and alteration of its physical properties. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Several other proteins known to signal via actin-regulatory pathways, including VCP/neurofibromin, NESH/Abi-3 and Cofilin, drive similar effects on spine structure when either up- or downregulated.

    “As we observe an increase in immature spines upon CYFIP1 overexpression or haploinsufficiency in vitro, it is interesting to note that several other proteins known to signal via actin-regulatory pathways have been shown to drive similar effects on spine structure when either up- or downregulated, including VCP/neurofibromin, NESH/Abi-3 and Cofilin.47,48,57,64, 65, 66, 67”

    From The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (2014) · cites this paper as [66]

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Cited by

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Authors
Hotulainen, P., Llano, O., Smirnov, S., Tanhuanpää, K., Faix, J., Rivera, C., & Lappalainen, P.
Affiliations
  • University of Helsinki (FI)
  • Medizinische Hochschule Hannover (DE)
Corresponding author
Hotulainen, Pirta
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2009-04-20
Volume
185
Issue
2
Pages
323-339
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200809046
PMC
PMC2700375
OpenAlex
W1980581068
Cited by
360
References
1
Citations by year
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FWCI
12.61
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords
dendritic spines, spine morphogenesis, actin polymerization, actin depolymerization, actin cytoskeleton, filopodia, Arp2/3 complex, actin nucleation, ADF/cofilin, actin filament disassembly, synaptic transmission, postsynaptic structures
MeSH terms
Actins, Animals, Microtubule-Associated Proteins, NADPH Dehydrogenase, Neurons, Pseudopodia, Recombinant Fusion Proteins, Telomere-Binding Proteins, RNA, Small Interfering, Dendritic Spines, Cofilin 1, Actin-Related Protein 2-3 Complex, Mice

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