1.H.2 The Invertebrate PMP22-Claudin (Claudin2) Family

Claudins are integral transmembrane components of tight junctions (TJs), forming trans-epithelial barriers in many organs, such as the nervous system, lungs and epidermis. In Drosophila, three claudins have been identified which are required for forming the TJ analogous structures - the septate junctions (SJs). The lack of claudins results in disruption of the integrity of the SJs, leading to the breakdown of the trans-epithelial barrier and disturbed epithelial morphogenesis. These homologues are involved in transport and membrane organization. They associate with over 100 proteins in the Drosophila proteome (Jaspers et al., 2012). Four of the proteins in 1.H.2.1.1 (Lachesin, Fasciclin, Neuroglian and Leukocyte-antigen related protiein) are distantly related to members of the Basigin Superfamily (see for example, TC family 8.A.23).

SJs evolved as cell-cell junctions (occluding junctions) that regulate the paracellular barrier and integrity of epithelia in invertebrates. Multiple morphological variants of SJs exist specific to different epithelia and/or phyla, but the biological significance of varied SJ morphology is unclear because the knowledge of the SJ associated proteins and their functions in non-insect invertebrates is largely unknown (Jonusaite et al. 2022). Genes encoding proteins that form SJs have been identified and tested in the model invertebrate, Drosophila melanogaster, which like other insects, and more generally arthropods, have two morphological SJ variants, the ectodermal pleated SJs (pSJs) in ectodermally derived epithelial cells and the endodermal smooth SJs (sSJs) in endodetmally derived epithelial cell, respectively (Izumi and Furuse 2014; Jonusaite et al. 2022). Identified components of the pSJs include:

1. Neuroglian, Neurexin IV and Contactin: membrane proteins conserved in vertebrate paranodal SJs, 1302 aas (P20241)
2. Na⁺/K⁺-ATPase, α-subunit (see TC# 3.A.3.1) 1041 aas (P13607)
3. Lachesin: a homophilic cell–cell adhesion protein, 359 aas (Q24372)
4. Megatrachea, Sinuous and Kune-kune: claudin family proteins, 986 aas (B3MI57)
5. Melanotransferrin: a GPI-anchored and iron-binding protein, 819 aas (Q9VTZ5)
6. Fasciclin II and Fasciclin III: homophilic cell–cell adhesion molecules, 873 aas (P34082); 508 aas (P15278), respectively
7. Macroglobulin complement-related: a protein involved in phagocytosis, 1760 aas, (P34082)
8. Gliotactin: a tricellular junctional component of pSJs, 956 aas (Q9NK80)
9. Coracle and Yurt: FERM proteins, CorA, 1698 aas (Q9V8R9); Yrt, 972 aas (Q9VFU8), respectively
10. Varicose: a MAGUK protein, Vari, 306 aas (A1XXK7)
11. Dlg, Lgl and Scribble: tumor suppressors and cell polarity regulators, Dlg7, 970 aas (P31007); Lgl, 1093 aas (M9PBJ2); ScriB, 1851 aas, (Q7KRY7), respectively
12. Leukocyte antigen 6 superfamily proteins, i.e., isoform I, 1941 aas (NP_001260597.1)
13. A lipid phosphate phosphatase, Wunen, Wun, 379 aas (Q9V576)
14. G-protein signaling-related proteins, i.e., Moody, 670 aas (Q9W534)

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