Essential Role for the PKC Target MARCKS in Maintaining Dendritic Spine Morphology
Open accessAbstract
Spine morphology is regulated by intracellular signals, like PKC, that affect cytoskeletal and membrane dynamics. We investigated the role of MARCKS (myristoylated, alanine-rich C-kinase substrate) in dendrites of 3-week-old hippocampal cultures. MARCKS associates with membranes via the combined action of myristoylation and a polybasic effector domain, which binds phospholipids and/or F-actin, unless phosphorylated by PKC. Knockdown of endogenous MARCKS using RNAi reduced spine density and size. PKC activation induced similar effects, which were prevented by expression of a nonphosphorylatable mutant. Moreover, expression of pseudophosphorylated MARCKS was, by itself, sufficient to induce spine loss and shrinkage, accompanied by reduced F-actin content. Nonphosphorylatable MARCKS caused spine elongation and increased the mobility of spine actin clusters. Surprisingly, it also decreased spine density via a novel mechanism of spine fusion, an effect that required the myristoylation sequence. Thus, MARCKS is a key factor in the maintenance of dendritic spines and contributes to PKC-dependent morphological plasticity.
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In vitro studies of hippocampal pyramidal cell cultures have shown that PKC phosphorylation of MARCKS induces collapse of the actin cytoskeleton by disconnecting actin from the neuronal membrane.
“In vitro studies of hippocampal pyramidal cell cultures have shown that PKC phosphorylation of MARCKS induces collapse of the actin cytoskeleton by disconnecting actin from the neuronal membrane96 (Fig. 4, gold).”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [96]
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- Authors
- Calabrese, B., & Halpain, S.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Halpain, Shelley
- ORCID
- Halpain, Shelley
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 48
- Issue
- 1
- Pages
- 77-90
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2009758415
- Cited by
- 187
- References
- 7
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 2 · 2022: 7 · 2021: 10 · 2020: 4 · 2019: 8 · 2018: 9 · 2017: 9 · 2016: 10 · 2015: 9 · 2014: 15 · 2013: 9 · 2012: 10
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2882 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH050861)
- National Institute of Neurological Disorders and Stroke (R01NS037311, NS37311)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- MARCKS, protein kinase C, dendritic spine morphology, myristoylation, F-actin, spinal fusion, spine density, spine plasticity, membrane binding
- MeSH terms
- Myristoylated Alanine-Rich C Kinase Substrate, Actins, Analysis of Variance, Animals, Cells, Cultured, Diagnostic Imaging, Embryo, Mammalian, Gene Expression Regulation, Hippocampus, Immunohistochemistry, Membrane Proteins, Models, Biological, Neuronal Plasticity, Neurons, Protein Kinase C, Synapses, Tetradecanoylphorbol Acetate, Time Factors, Transfection, Fluoroimmunoassay, Mutagenesis, Synaptophysin, Presynaptic Terminals, Patch-Clamp Techniques, Excitatory Postsynaptic Potentials, RNA, Small Interfering, Intracellular Signaling Peptides and Proteins, Dendritic Spines, Green Fluorescent Proteins, Rats
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