ArticleNature communications2014
A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
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- Are Methylation Patterns in theInternational journal of molecular sciences · 2024Article
- Medial prefrontal neuroplasticity during extended-release naltrexone treatment of opioid use disorder - a longitudinal structural magnetic resonance imaging study.Translational psychiatry · 2024Article
- A Novel Cis-Regulatory lncRNA,Non-coding RNA · 2023Article
- The meLife · 2022Article
- A developmental delay linked missense mutation in Kalirin-7 disrupts protein function and neuronal morphology.Frontiers in molecular neuroscience · 2022Article
- Review
- Establishing functional lentiviral vector production in a stirred bioreactor for CAR-T cell therapy.Bioengineered · 2021Article
- Review
- Rapid 3D Enhanced Resolution Microscopy Reveals Diversity in Dendritic Spinule Dynamics, Regulation, and Function.Neuron · 2020Article
- Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction.Cell reports · 2020Article
- Kalirin and Trio: RhoGEFs in Synaptic Transmission, Plasticity, and Complex Brain Disorders.Trends in neurosciences · 2020Review
- Article
- Current challenges and possible future developments in personalized psychiatry with an emphasis on psychotic disorders.Heliyon · 2020Review
- Synaptic Kalirin-7 and Trio Interactomes Reveal a GEF Protein-Dependent Neuroligin-1 Mechanism of Action.Cell reports · 2019Article
- Dendritic structural plasticity and neuropsychiatric disease.Nature reviews. Neuroscience · 2018Review
- A Schizophrenia-Linked KALRN Coding Variant Alters Neuron Morphology, Protein Function, and Transcript Stability.Biological psychiatry · 2018Article
- An autism spectrum disorder-related de novo mutation hotspot discovered in the GEF1 domain of Trio.Nature communications · 2017Article
- Brain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity.ACS chemical neuroscience · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability to catalyse the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. Consistent with this, mice with reduced kalirin expression showed reduced neuropil volume in the rodent homologue of the STS. These data suggest that single amino acid changes in proteins involved in dendritic spine function can have significant effects on the structure and function of the cerebral cortex.
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