Gap junctions contain hydrophilic membrane channels that allow direct communication between neighboring cells through the diffusion of ions, metabolites, and small cell signaling molecules. They are made up of a hexameric array of polypeptides encoded by the connexin multi-gene family. Cell-cell communication mediated by connexins is crucial to various cellular functions, including the regulation of cell growth, differentiation, and development. Mutations in connexin genes have been linked to a variety of human diseases, including cardiovascular anomalies, peripheral neuropathy, deafness, skin disorders, and cataracts. In addition to their coupling function, recent studies suggest that connexin proteins may also mediate signaling. This could involve interactions with other protein partners that may play a role not only in connexin assembly, trafficking, gating and turnover, but also in the coordinate regulation of cell-cell communication with cell adhesion and cell motility. The integration of these cell functions is likely to be important in the role of gap junctions in development and disease.

Vaccination represents an efficient and cost-effective way to contain influenza epidemics and preserve public health. Since their introduction in the 1940s, seasonal influenza vaccines have saved countless lives and limited pandemic spread. Influenza viruses nonetheless continue to evolve through genetic mutation and escape from natural immunity, and vaccines must be updated yearly. The protective efficacy of the current licensed vaccines varies each year (Fig. 1a), depending on the antigenic match between circulating viruses and vaccine strains. The immune status of the host can also affect vaccine efficacy. For example, young and elderly individuals are more susceptible to the complications of influenza infection [1][2][3] .New influenza viruses have precipitated pandemics several times over the past 100 years, specifically in 1918, 1957, 1968 and 2009 (reF. 4 ). The threat of the reemergence of old pandemic viruses and the emergence of novel viruses with pandemic potential underscore the need for durable and broadly protective influenza vaccines. Advances in immunology and virology, together with information from structural biology and bioinformatics, are facilitating the development of novel vaccine approaches [5][6][7][8] . Of particular interest are human broadly neutralizing antibodies directed to conserved viral structures. These antibodies arise naturally and can also be elicited through immunization .Current licensed influenza vaccines contain either in activated or live attenuated influenza viruses. Most in activated vaccines consist of split viruses or subunit influenza antigens (Table 1). Split vaccines are produced by disrupting viral particles with chemicals or detergents Haemagglutinin (Ha). a homotrimeric glycoprotein found on the surface of influenza virus particles responsible for the recognition of the host target cell through the binding of sialic acid-containing receptors.

Previous studies have indicated an intimate linkage between gap junction and adherens junction formation. It was suggested this could reflect the close membranemembrane apposition required for junction formation. In NIH3T3 cells, we observed the colocalization of connexin43 (Cx43␣1) gap junction protein with N-cadherin, p120, and other N-cadherin-associated proteins at regions of cell-cell contact. We also found that Cx43␣1, N-cadherin, and N-cadherin-associated proteins were coimmunoprecipitated by antibodies to either Cx43␣1, N-cadherin, or various N-cadherin-associated proteins. These findings suggest that Cx43␣1 and N-cadherin are coassembled in a multiprotein complex containing various N-cadherin-associated proteins. Studies using siRNA knockdown indicated that cell surface expression of Cx43␣1 required N-cadherin, and conversely, Ncadherin cell surface expression required Cx43␣1. Pulse-chase labeling and cell surface biotinylation experiments indicated that in the absence of N-cadherin, Cx43␣1 cell surface trafficking is blocked. Surprisingly, siRNA knockdown of p120, an N-cadherin-associated protein known to modulate cell surface turnover of Ncadherin, reduced N-cadherin cell surface expression without altering Cx43␣1 expression. These observations suggest that in contrast to the coregulated cell surface trafficking of Cx43␣1 and N-cadherin, N-cadherin turnover at the cell surface may be regulated independently of Cx43␣1. Functional studies showed gap junctional communication is reduced and cell motility inhibited with N-cadherin or Cx43␣1 knockdown, consistent with the observed loss of both gap junction and cadherin contacts with either knockdown. Overall, these studies indicate that the intracellular coassembly of connexin and cadherin is required for gap junction and adherens junction formation, a process that likely underlies the intimate association between gap junction and adherens junction formation.