The Stories We Tell

These voices you will hear in this edition of First Gen Voices were crafted and cultivated in a summer trip to the Dominican Republic, where our writers had the opportunity to workshop and reflect on their experiences being first-generation. The purpose? To share their work, mind, and feelings about the struggles and incredible experiences they have made. It is their strength, resilience, and love. Enjoy

Pannexin 1 binds β-catenin to modulate melanoma cell growth and metabolism

Melanoma is the most aggressive skin malignancy with increasing incidence worldwide. Pannexin1 (PANX1), a member of the pannexin family of channel-forming glycoproteins, regulates cellular processes in melanoma cells including proliferation, migration, and invasion/metastasis. However, the mechanisms responsible for coordinating and regulating PANX1 function remain unclear. Here, we demonstrated a direct interaction between the C-terminal region of PANX1 and the N-terminal portion of β-catenin, a key transcription factor in the Wnt pathway. At the protein level, β-catenin was significantly decreased when PANX1 was either knocked down or inhibited by two PANX1 blockers, Probenecid and Spironolactone. Immunofluorescence imaging showed a disrupted pattern of β-catenin localization at the cell membrane in PANX1-deficient cells, and transcription of several Wnt target genes, including MITF, was suppressed. In addition, a mitochondrial stress test revealed that the metabolism of PANX1-deficient cells was impaired, indicating a role for PANX1 in the regulation of the melanoma cell metabolic profile. Taken together, our data show that PANX1 directly interacts with β-catenin to modulate growth and metabolism in melanoma cells. These findings provide mechanistic insight into PANX1-mediated melanoma progression and may be applicable to other contexts where PANX1 and β-catenin interact as a potential new component of the Wnt signaling pathway

Live. Tell. Resist.

This edition of First-Gen Voices features the stories and work of 24 first-generation college students at multiple higher education institutions. The aim is to disseminate a story about us, for us, and consequently, the dominant cultures that have yet to learn from our power

Simvastatin Sodium Salt and Fluvastatin Interact with Human Gap Junction Gamma-3 Protein

Finding pleiomorphic targets for drugs allows new indications or warnings for treatment to be identified. As test of concept, we applied a new chemical genomics approach to uncover additional targets for the widely prescribed lipid-lowering pro-drug simvastatin. We used mRNA extracted from internal mammary artery from patients undergoing coronary artery surgery to prepare a viral cardiovascular protein library, using T7 bacteriophage. We then studied interactions of clones of the bacteriophage, each expressing a different cardiovascular polypeptide, with surface-bound simvastatin in 96-well plates. To maximise likelihood of identifying meaningful interactions between simvastatin and vascular peptides, we used a validated photo-immobilisation method to apply a series of different chemical linkers to bind simvastatin so as to present multiple orientations of its constituent components to potential targets. Three rounds of biopanning identified consistent interaction with the clone expressing part of the gene GJC3, which maps to Homo sapiens chromosome 7, and codes for gap junction gamma-3 protein, also known as connexin 30.2/31.3 (mouse connexin Cx29). Further analysis indicated the binding site to be for the N-terminal domain putatively ‘regulating’ connexin hemichannel and gap junction pores. Using immunohistochemistry we found connexin 30.2/31.3 to be present in samples of artery similar to those used to prepare the bacteriophage library. Surface plasmon resonance revealed that a 25 amino acid synthetic peptide representing the discovered N-terminus did not interact with simvastatin lactone, but did bind to the hydrolysed HMG CoA inhibitor, simvastatin acid. This interaction was also seen for fluvastatin. The gap junction blockers carbenoxolone and flufenamic acid also interacted with the same peptide providing insight into potential site of binding. These findings raise key questions about the functional significance of GJC3 transcripts in the vasculature and other tissues, and this connexin’s role in therapeutic and adverse effects of statins in a range of disease states

Concise review of the genus Solieria J. Agardh, 1842

International audienceSolieria spp. (Solieriaceae, Gigartinales, Rhodophyta) can be found in various habitats ranging from the marine environment to low-salinity estuarine environments. Of the commercially exploited carrageenophytes, some of the most abundant belong to the Solieriaceae family as, Kappaphycus, Eucheuma and Solieria. The supply of these seaweeds is ensured by their mastered culture and by large quantities of stranded wild seaweeds which are harvested. Rich in carrageenans, i.e., in linear sulfated galactans, these red macroalgae are widely used for their gelling, thickening, and stabilizing properties in food, cosmetic, or pharmaceutical industries. In addition, Solieria spp. provide scientific potential as a model for the development of cultures in Integrated Multitrophic Aquaculture (IMTA), for innovation in extraction and purification processes and in biorefineries to access to bioactive compounds. The genus Solieria was described using the species Solieria chordalis as the type species in 1842. Today, this species is found in large quantities on the beaches of the western Atlantic just like Solieria filiformis found on the other side of the Ocean on some beaches in Mexico. Due to its abundance, several scientific teams from France and from Mexico study these algae with high potential in nutrition, health and for environmental applications. Eight other species of the genus Solieria have been inventoried, the last one in 2018. Nevertheless, their abundance is lower as well as the number of scientific studies mentioning them. Therefore, in this review, we focus on the biology, ecophysiology, biochemical composition, and applications of Solieria spp. based mainly on the two species widely studied, namely Solieria chordalis and Solieria filiformis

Gap Junctions

Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981-2035, 2012