Dr. Trond Aasen, principal investigator of the Molecular Pathology group at Vall d’Hebron Institute of Research (VHIR), has identified how is regulated connexin 43, which is the most widely expressed gap junction protein, and how several protein isoforms can be translated from a single mRNA transcript. The study has been recently published in " "http://www.biosignaling.com/content/12/1/31" Cell Communication and Signaling.Direct communication between adjacent cells is mediated through gap junction channels, a process critical for embryonic development and tissue homeostasis. Connexin 43 has been implicated in a number of important diseases including cancer, cardiac disease and neuronal disorders and its mutations also causes oculodentodigital dysplasia, a multifaceted rare syndromic disease. Connexin 43 is generated from a single mRNA transcript and normally resides in the cell membrane but protein expression levels and subcellular localization are frequently altered in many pathological conditions. The study demonstrates that internal translation of the gene transcript occurs, generating smaller protein isoforms that do not target to the cell membrane. “Surprisingly, we have shown that translation is cap-dependent and not due to a classical IRES-dependent mechanism”, reports Dr. Aasen. He has also demonstrated that the kinases Mnk1/2, in addition to the mTOR kinase, can regulate the ratio between full-lenght protein and the smaller isoforms. The Molecular Pathology group, led by Dr. Santiago Ramon i Cajal, is now correlating the activation of these pathways with the subcellular reorganization of connexin 43 that frequently occurs during cancer development. The lab is also continuing to elucidate how internal translation is mediated, which may answer key questions on how increased protein divesity is generated from a single RNA transcript.