γ-Protocadherins Control Cortical Dendrite Arborization by Regulating the Activity of a FAK/PKC/MARCKS Signaling Pathway
Open accessAbstract
The 22 γ-protocadherins (γ-Pcdhs) potentially specify thousands of distinct homophilic adhesive interactions in the brain. Neonatal lethality of mice lacking the Pcdh-γ gene cluster has, however, precluded analysis of many brain regions. Here, we use a conditional Pcdh-γ allele to restrict mutation to the cerebral cortex and find that, in contrast to other central nervous system phenotypes, loss of γ-Pcdhs in cortical neurons does not affect their survival or result in reduced synaptic density. Instead, mutant cortical neurons exhibit severely reduced dendritic arborization. Mutant cortices have aberrantly high levels of protein kinase C (PKC) activity and of phosphorylated (inactive) myristoylated alanine-rich C-kinase substrate, a PKC target that promotes arborization. Dendrite complexity can be rescued in Pcdh-γ mutant neurons by inhibiting PKC, its upstream activator phospholipase C, or the γ-Pcdh binding partner focal adhesion kinase. Our results reveal a distinct role for the γ-Pcdhs in cortical development and identify a signaling pathway through which they play this role.
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Pcdhs have been reported to regulate actin filament activity.
“Since Pcdhs have been reported to regulate actin filament activity (Chen et al., 2009;Garrett et al., 2012;Keeler et al., 2015)”
From Cell Adhesion Molecule Protocadherin-γC5 Ameliorates Aβ Plaque Pathogenesis by Modulating Astrocyte Function in Alzheimer's Disease (2025) · cites this paper as Garrett et al., 2012
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- Authors
- Garrett, A. M., Schreiner, D., Lobas, M. A., & Weiner, J. A.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Weiner, Joshua A.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 74
- Issue
- 2
- Pages
- 269-276
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3582349
- OpenAlex
- W1983845889
- Cited by
- 165
- References
- 1
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 13 · 2022: 7 · 2021: 15 · 2020: 11 · 2019: 12 · 2018: 14 · 2017: 13 · 2016: 14 · 2015: 16 · 2014: 7 · 2013: 11 · 2012: 3
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS055272)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- gamma-protocadherins, dendritic branching, cortical neurons, focal adhesion kinase, protein kinase C, MARCKS, phospholipase C, homophilic adhesion, conditional knockout, cortical development
- MeSH terms
- Cadherin Related Proteins, Myristoylated Alanine-Rich C Kinase Substrate, Empty Spiracles Homeobox Proteins, Age Factors, Animals, Animals, Newborn, Bacterial Proteins, Cells, Cultured, Cerebral Cortex, Dendrites, Luminescent Proteins, Membrane Proteins, Mice, Transgenic, Neurons, Protein Kinase C, Transcription Factors, Transfection, Signal Transduction, Cadherins, Sequence Deletion, Homeodomain Proteins, Gene Expression Regulation, Developmental, Intracellular Signaling Peptides and Proteins, Mice, Focal Adhesion Kinase 1
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