Abstract
This review highlights current knowledge on the expression and function of connexins and pannexins, transmembrane channel proteins that play an important role in intercellular communication, in both the developing and mature lymphatic vasculature. A particular focus is given to the involvement of these proteins in functions of the healthy lymphatic system. We describe their influence on the maintenance of extracellular fluid homeostasis, immune cell trafficking to draining lymph nodes and dietary nutrient absorption by intestinal villi. Moreover, new insights into connexin mutations in primary and secondary lymphedema as well as on the implication of lymphatic connexins and pannexins in acquired cardiovascular diseases are discussed, allowing for a better understanding of the role of these proteins in pathologies linked to dysfunctions in the lymphatic system.
Highlights
Twenty one gap junction proteins, called connexins (Cxs), are found in humans, compared to twenty in mice [1,2]
Cx26breast expression in was associated with lymphatic vessel invasion [33]. These findings suggest an involvement of ectodermal/epithelial Cx26 in the signaling regulating lymphangiogenesis, it should be kept in mind that expression of Cx26 in the lymphatic endothelial cells (LECs) themselves has never been demonstrated
Cx-built gap junction channels have been considered for over 50 years as integral components for cell-to-cell coupling within the cardiovascular system, and Panx channels have been more recently added to this repertoire of proteins for intercellular communication
Summary
Twenty one gap junction proteins, called connexins (Cxs), are found in humans, compared to twenty in mice [1,2]. Gap junction channels are formed by the docking of connexons from two adjacent cells, allowing the diffusion of small molecules (< 1 kDa) and ions between their cytoplasms [4,5]. Another family of transmembrane proteins, called pannexins (Panxs), share the same topology as Cxs but with different sequences. This family of channel-forming proteins consists of only three members, namely Panx1–Panx3 [6].
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