A Role of Pannexins in the Development of the Astrocytic Tumors

Project leader: Yvette Connell-Alberts

This is a collaborative project with the lab of Dr. K. Reilly (NCI Frederick)

Connexins had been considered to be the only class of the vertebrate proteins capable of gap junction formation, however, new candidates for this function with no homology to connexins, termed pannexins were discovered. So far three pannexins were described in mouse and human genomes: Panx1, Panx2 and Panx3. Expressions of pannexins can be detected in numerous brain structures and in the retina. Among suggested pannexin functions are their involvement in electrical synapses generating synchronous activity in the hippocampus and neocortex and the propagation of the calcium waves. These functions may be mutually regulated, as there are indications that unpaired and docked pannexins coexist in the membrane. In addition to the role in the electrical synapses and in the calcium wave propagation, pannexins may play a role in ischemia. Despite the prominent pannexin-specific staining of neurons, the question of their cell specificity is still unclear as some indirect evidences point out that pannexin mRNAs might be present in some glial cells.

High-throughput studies produced some evidences of the pannexin involvement in the process of tumorigenesis. According to brain cancer gene expression database REMBRANDT, PANX2 expression levels can predict post diagnosis survival for patients with glial tumors. As human PANX2 gene is located within chromosomal region 22q13.3 that is often deleted in human astrocytomas and ependymomas, this pannexin could be viewed as a candidate for tumor suppressor gene involved in gliomagenesis. Further investigations are needed to verify or reject these hypotheses.