Connexins in lymphatic vessel physiology and disease.
Connexins are transmembrane proteins that form gap junction- and hemi-channels. Once inserted into the membrane, hemi-channels (connexons) allow for diffusion of ions and small molecules (<1 kDa) between the extracellular space and the cytosol. Gap junction channels allow diffusion of similar molecules between the cytoplasms of adjacent cells. The expression and function of connexins in blood vessels has been intensely studied in the last few decades. In contrast, only a few studies paid attention to lymphatic vessels; convincing in vivo data with respect to expression patterns of lymphatic connexins and their functional roles have only recently begun to emerge. Interestingly, mutations in connexin genes have been linked to diseases of lymphatic vasculature, most notably primary and secondary lymphedema. This review summarizes the available data regarding lymphatic connexins. More specifically it addresses (i) early studies aimed at presence of gap junction-like structures in lymphatic vessels, (ii) more recent studies focusing on lymphatic connexins using genetically engineered mice, and (iii) results of clinical studies that have reported lymphedema-linked mutations in connexin genes.
Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland; Department of Internal Medicine - Cardiology, University of Geneva, CH-1211 Geneva, Switzerland.
Merlijn J
MJ
Meens
Department of Oncology, University Hospital of Lausanne, 1066 Epalinges, Switzerland; Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
Amélie
A
Sabine
Department of Oncology, University Hospital of Lausanne, 1066 Epalinges, Switzerland; Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland; École Polytechnique Fédérale de Lausanne (EPFL), Swiss Institute for Experimental Cancer Research (ISREC), 1015 Lausanne, Switzerland.
Tatiana V
TV
Petrova
Department of Pathology and Immunology, University of Geneva, CH-1211 Geneva, Switzerland; Department of Internal Medicine - Cardiology, University of Geneva, CH-1211 Geneva, Switzerland. Electronic address: brenda.kwakchanson@unige.ch.
Brenda R
BR
Kwak
D000818:Animals; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000473:pathology; D008209:Lymphedema / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation
D017630:Connexins
Connexin; Endothelial cell; Gap junction; Lymphedema