Abnormal Spine Morphology and Enhanced LTP in LIMK-1 Knockout Mice
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In vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphorylation and actin dynamics. In addition, abnormal expression of LIMK-1 is associated with Williams syndrome, a mental disorder with profound deficits in visuospatial cognition. However, the in vivo function of this family of kinases remains elusive. Using LIMK-1 knockout mice, we demonstrate a significant role for LIMK-1 in vivo in regulating cofilin and the actin cytoskeleton. Furthermore, we show that the knockout mice exhibited significant abnormalities in spine morphology and in synaptic function, including enhanced hippocampal long-term potentiation. The knockout mice also showed altered fear responses and spatial learning. These results indicate that LIMK-1 plays a critical role in dendritic spine morphogenesis and brain function.
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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 [65]
The Results report altered spine shape in LIMK-1 knockout mice, and the Discussion links LIMK-1 to cofilin phosphorylation and actin dynamics. This supports a cofilin-related pathway affecting spine structure, but the study did not up- or downregulate cofilin itself; it reports unchanged total cofilin. It does not address VCP/neurofibromin or NESH/Abi-3. (LLM, conf=0.86)
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- Authors
- Meng, Y., Zhang, Y., Tregoubov, V., Janus, C., Cruz, L., Jackson, M., Lu, W.-Y., MacDonald, J. F., Wang, J. Y., Falls, D. L., & Jia, Z.
- Affiliations
- Hospital for Sick Children (CA)
- University of Toronto (CA)
- Emory University (US)
- Corresponding author
- Jia, Zhengping
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 35
- Issue
- 1
- Pages
- 121-133
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2028363992
- Cited by
- 688
- References
- 6
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 16 · 2023: 17 · 2022: 17 · 2021: 21 · 2020: 18 · 2019: 15 · 2018: 26 · 2017: 40 · 2016: 26 · 2015: 32 · 2014: 42 · 2013: 38 · 2012: 32
- FWCI
- 12.13
- 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, 4034 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
- Hospital for Sick Children
- National Institutes of Health
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Keywords
- LIM kinase, cofilin phosphorylation, actin cytoskeleton, dendritic spine morphology, spine morphogenesis, long-term potentiation, hippocampus, synaptic function, Williams syndrome, fear response, spatial learning, knockout mice
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Conditioning, Psychological, Cytoskeleton, Dendrites, DNA-Binding Proteins, Fear, Female, Hippocampus, Male, Microfilament Proteins, Actin Cytoskeleton, Microtubule-Associated Proteins, Motor Activity, Mutation, Nervous System Malformations, Neural Inhibition, Protein Kinases, Up-Regulation, Protein Serine-Threonine Kinases, Long-Term Potentiation, Mice, Knockout, Maze Learning, Williams Syndrome, Excitatory Postsynaptic Potentials, Actin Depolymerizing Factors, Mice, Lim Kinases
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