Abstract
Occluding cell-cell junctions are pivotal during the development of many organs. One example is septate junction (SJ) strands, which are found in vertebrates and invertebrates. Although several proteins have been identified that are responsible for septate junction formation in Drosophila, it is presently unclear how these structures are formed or how they are positioned in a coordinated manner between two neighboring cells and within the tissue. Here, we identified a GPI-anchored protein called Undicht required for septate junction formation. Clonal analysis and rescue experiments show that Undicht acts in a non-cell-autonomous manner. It can be released from the plasma membrane by the proteolytic activity of two related ADAM10-like proteases, Kuzbanian and Kuzbanian-like. We propose that juxtacrine function of Undicht coordinates the formation of septate junction strands on two directly neighboring cells, whereas paracrine activity of Undicht controls the formation of occluding junctions within a tissue.
Highlights
Epithelial and endothelial cells establish barriers that separate body compartments with distinct metabolic properties
Insects developed an additional layer of complexity by adding pleated septate junctions (SJs) to the interdigitating glial cell processes that seal off two facing cells (Limmer et al, 2014; Babatz et al, 2018; Tepass et al, 2001)
Identification of undicht To date, 23 membrane-associated proteins are identified as septate junction proteins (Table S1) and additional candidates were identified in further screens (Jaspers et al, 2012; J.P., unpublished data)
Summary
Epithelial and endothelial cells establish barriers that separate body compartments with distinct metabolic properties. Higher vertebrates establish tight junctions to tightly connect two neighboring cells. These junctions are found in epithelia and in BBB forming endothelial cells (Tietz and Engelhardt, 2015). Glial cells establish a diffusion barrier by intensive interdigitations that increase the diffusion length for all solutes (Bundgaard and Abbott, 2008). Invertebrates, such as snails, use a similar strategy. Glial cells establish the BBB by forming highly interdigitating cell-cell connections (Bundgaard and Abbott, 1992). Morphologically as well as molecularly similar structures are established between glial cells and axonal membranes in the paranodal junctions (Girault and Peles, 2002)
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