Abstract
A major class of tetraspanins are uroplakins (UP’s) Ia and Ib that, together with their associated (non-tetraspanin) uroplakins II and IIIa, form two dimensional crystals of 16-nm particles, known as ‘urothelial plaques’. Interconnected by small hinge areas, urothelial plaques cover almost the entire apical surface of mammalian bladder urothelium, and contribute to the remarkable urothelial permeability barrier function. UPIa and Ib bind selectively to UPII and IIIa, respectively, to form a UPIa/II and UPIb/IIIa heterodimer, which constitutes one of the six dumbbell-shaped, heterotetramer subunit of a stellate-shaped 16-nm uroplakin particle. Ultrastructural studies indicate that UPIa/II and UPII/IIIa dimers are associated with the inner and outer subdomains of the 16-nm particles, respectively. In vitro gel overlay assay suggests that the high mannose glycan anchored on the second, large extracellular loop of UPIa may serve as the urothelial receptor for the type 1-fimbriated E. coli that causes over 85% of urinary tract infection. Moreover, uroplakin defects may play a role in renal adysplasia and overreactive bladder. Although uroplakins are expressed mainly as major differentiation products of bladder urothelium, small amounts of uroplakins are present in some nonurothelial tissues including oocytes and may play a diverse range of important biological functions.
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Acknowledgments
We thank our collaborators who contributed to this work, including Ueli Abei (University of Basel, Switzerland), Gerard Apodaca (University of Pittsburgh Medical School), George Christ (Wake Forest University), Cathy Costello (Boston University Medical School), Robert DeSalle (American Museum of Natural History), Garth Ehrlich (Drexel University Medical School), Antonio Garcia-Expana (Universitat Rovira i Virgili, Tarragona, Spain), Bechara Kachar (NIDCD, National Institutes of Health), David Klumpp (Northwestern University Medical School), David Sabatini and Ellen Shapiro (NYU Medical School), Francis Schneck (University of Pittsburgh), Jun Yu (Beijing Genomic Institute) and Mark Zeidel (Harvard Medical School). This work was supported by NIH grants DK52206, DK39753, DK69688; a Merit Review Award from the Veterans Affairs Administration; and a grant-in-aid from the Goldstein Fund for Urological Research of the New York University School of Medicine.
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Sun, TT., Kreibich, G., Pellicer, A., Kong, XP., Wu, XR. (2013). Uroplakins as Unique Tetraspanin Networks. In: Berditchevski, F., Rubinstein, E. (eds) Tetraspanins. Proteins and Cell Regulation, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6070-7_12
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