Kalirin loss results in cortical morphological alterations
Open accessAbstract
Morphogenesis of pyramidal neuronal dendrites and spines is crucial for the formation and refinement of forebrain neuronal circuits underlying cognition. Aberrant dendrite and spine morphology is associated with neuropathological disorders. However, the molecular mechanisms controlling pyramidal neuronal dendrite and spine morphogenesis in vivo remain largely unknown. Kalirin is a brain-specific guanine-nucleotide exchange factor for Rho-like small GTPases, and an important regulator of spine morphogenesis in cultured neurons. Here we show that RNAi-dependent knockdown of kalirin in cultured neurons affected dendrite morphology. Cortical pyramidal neurons from KALRN-null mice showed reduced spine density and impaired activity-dependent spine plasticity; and they exhibited reduced complexity of dendritic trees. KALRN-null mice also displayed smaller neuronal cell bodies and reductions in the size of the cortex and cortical layers. These data demonstrate important roles for kalirin in the regulation of cortical structure, ultrastructure, and spine structural plasticity.
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Kalrn knockout mice exhibit schizophrenia-related deficits in working memory, sociability, and prepulse inhibition.
“Notably, Kalrn−/− mice show severe reductions in spine density and dendrite complexity in the frontal cortex, as well as schizophrenia-related impairments in working memory, sociability and prepulse inhibition92,93.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [93]
Kalrn knockout mice have severely reduced spine density and dendrite complexity in the frontal cortex.
“Notably, Kalrn−/− mice show severe reductions in spine density and dendrite complexity in the frontal cortex, as well as schizophrenia-related impairments in working memory, sociability and prepulse inhibition92,93.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [93]
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Dendritic spine pathology in neuropsychiatric disorders
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- Authors
- Xie, Z., Cahill, M. E., & Penzes, P.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Penzes, Peter
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 43
- Issue
- 1
- Pages
- 81-89
- ISSN
- 1044-7431 (ISSN-L)
- PMC
- PMC2818244
- OpenAlex
- W2092315684
- Cited by
- 56
- References
- 56
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 3
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (F31AG031621)
- National Institute of Mental Health (R01MH071316)
- National Institute of Neurological Disorders and Stroke (T32NS041234)
- 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 › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- Kalirin, KALRN, dendrite morphogenesis, dendritic spines, spine plasticity, pyramidal neurons, cortical development, Rho GTPase guanine nucleotide exchange factor, neuronal ultrastructure
- MeSH terms
- Animals, Cells, Cultured, Cerebral Cortex, Dendrites, Humans, Male, Morphogenesis, Neuronal Plasticity, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Pyramidal Cells, Receptors, AMPA, Mice, Knockout, Guanine Nucleotide Exchange Factors, RNA Interference, Mice
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