Overexpression of protocadherin 7 inhibits neuronal survival by downregulating BIRC5 in vitro

Protocadherins (Pcdhs) are widely-expressed transmembrane proteins in the nervous system. Recent studies suggest that Pcdhs play multiple critical roles during neuronal development. However, the cellular mechanisms of Pcdh7 in neurons are still largely unknown. In the current study, we demonstrated that the expression of Pcdh7 during mouse brain development was regulated spatiotemporally. We observed that the elevated expression of Pcdh7 led to activation of the intrinsic apoptotic pathway in primary cortical neurons. Whole transcriptome sequencing revealed that 12 genes were involved in the apoptotic pathway including baculoviral inhibitor of apoptosis (IAP) repeat containing 5 (BIRC5). The neuronal apoptosis caused by Pcdh7 overexpression could be significantly inhibited by either a missense mutation in the conserved motif CM2 domain of Pcdh7 or BIRC5 overexpression. These results suggest the existence of Pcdh7-BIRC5 signaling cascade in the cortical neurons and represent a potential therapeutic area for further investigation.