Expression of Protocadherin-γC4 protein in the rat brain.

It has been proposed that the combinatorial expression of gamma-protocadherins (Pcdh-gamma s) 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-gamma family, for which experimental evidence derived from Pcdh-gamma-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-gamma family (Pcdh-gamma C3, Pcdh-gamma C4, and Pcdh-gamma C5) shows a phenotype similar to the mouse deficient in whole Pcdh-gamma family, indicating that the latter is largely due to the absence of C-type Pcdh-gamma s. The role of each individual C-type Pcdh-gamma is not known. We have developed a specific antibody to Pcdh-gamma C4 to reveal the expression of this protein in the rat brain. The results show that although Pcdh-gamma C4 is expressed at higher levels in the embryo and earlier postnatal weeks, it is also expressed in the adult rat brain. Pcdh-gamma C4 is expressed in both neurons and astrocytes. In the adult brain, the regional distribution of Pcdh-gamma C4 immunoreactivity is similar to that of Pcdh-gamma C4 mRNA, being highest in the olfactory bulb, dentate gyrus, and cerebellum. Pcdh-gamma C4 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-gamma C4 in neurons and astrocytes.