Expression of protocadherin‐γC4 protein in the rat brain

Abstract

It has been proposed that the combinatorial expression of γ‐protocadherins (Pcdh‐γs) and other clustered protocadherins (Pcdhs) provides a code of molecular identity and individuality to neurons, which plays a major role in the establishment of specific synaptic connectivity and formation of neuronal circuits. Particular attention has been directed to the Pcdh‐γ family, for which experimental evidence derived from Pcdh‐γ‐deficient mice shows that they are involved in dendrite self‐avoidance, synapse development, dendritic arborization, spine maturation, and prevention of apoptosis of some neurons. Moreover, a triple‐mutant mouse deficient in the three C‐type members of the Pcdh‐γ family (Pcdh‐γC3, Pcdh‐γC4, and Pcdh‐γC5) shows a phenotype similar to the mouse deficient in whole Pcdh‐γ family, indicating that the latter is largely due to the absence of C‐type Pcdh‐γs. The role of each individual C‐type Pcdh‐γ is not known. We have developed a specific antibody to Pcdh‐γC4 to reveal the expression of this protein in the rat brain. The results show that although Pcdh‐γC4 is expressed at higher levels in the embryo and earlier postnatal weeks, it is also expressed in the adult rat brain. Pcdh‐γC4 is expressed in both neurons and astrocytes. In the adult brain, the regional distribution of Pcdh‐γC4 immunoreactivity is similar to that of Pcdh‐γC4 mRNA, being highest in the olfactory bulb, dentate gyrus, and cerebellum. Pcdh‐γC4 forms puncta that are frequently apposed to glutamatergic and GABAergic synapses. They are also frequently associated with neuron‐astrocyte contacts. The results provide new insights into the cell recognition function of Pcdh‐γC4 in neurons and astrocytes.

Deletion of Protocadherin Gamma C3 Induces Phenotypic and Functional Changes in Brain Microvascular Endothelial Cells In Vitro

“…γ-Pcdhs also have three C-like variable exons that are expressed in neurons (Kaneko et al, 2006;Phillips et al, 2017). Mice lacking one of the γ-Pcdh-C3, C4 or C5 isoforms died due to neuronal apoptosis, similar to mice lacking all γ-Pcdhs, suggesting that these C-type-isoforms play a special role in the neuronal survival (Chen et al, 2012;Peek et al, 2017;Miralles et al, 2020).…”

Selective Overexpression of Collybistin in Mouse Hippocampal Pyramidal Cells Enhances GABAergic Neurotransmission and Protects against PTZ-Induced Seizures

“…Brains were cryoprotected with 30% sucrose, frozen, and sectioned with a freezing microtome (25 μm thick) and stored in 0.02% sodium azide in 0.1 M PB, pH 7.4 at 4 °C. Immunofluorescence was performed as described elsewhere (Li et al, 2005a;Fekete et al, 2017;Miralles et al, 2020). Briefly, free-floating brain sections were incubated with 5% normal goat serum, 0.3% Triton X-100 in 0.1 M PB for 1 hour at room temperature.…”

Wiring the Brain by Clustered Protocadherin Neural Codes

“…Clustered Pcdhs are widely expressed in the developing and adult central nervous systems [11,34,35,42,53,[87][88][89][90]. The expression of members of the Pcdha cluster is highly specific to the central nervous system.…”

“…While members of the Pcdh β and γ clusters are prominently expressed in the central nervous system, they are also expressed in several other tissues such as the kidney and lung [ 87 , 89 , 91 ]. Detailed expression patterns of each isoform were initially analyzed by in situ hybridization using isoform-specific probes, which showed that they are stochastically expressed in neuronal subpopulations in various brain nuclei or regions [ 35 , 42 , 53 , 89 , 90 , 92 ].…”