@article{KooMatthewsHarrisonetal.2022,
  author    = {Koo, Chek Ziu and Matthews, Alexandra L. and Harrison, Neale and Szyroka, Justyna and Nieswandt, Bernhard and Gardiner, Elizabeth E. and Poulter, Natalie S. and Tomlinson, Michael G.},
  title     = {The platelet collagen receptor GPVI is cleaved by Tspan15/ADAM10 and Tspan33/ADAM10 molecular scissors},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {5},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23052440},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284468},
  year      = {2022},
  abstract  = {The platelet-activating collagen receptor GPVI represents the focus of clinical trials as an antiplatelet target for arterial thrombosis, and soluble GPVI is a plasma biomarker for several human diseases. A disintegrin and metalloproteinase 10 (ADAM10) acts as a 'molecular scissor' that cleaves the extracellular region from GPVI and many other substrates. ADAM10 interacts with six regulatory tetraspanin membrane proteins, Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 and Tspan33, which are collectively termed the TspanC8s. These are emerging as regulators of ADAM10 substrate specificity. Human platelets express Tspan14, Tspan15 and Tspan33, but which of these regulates GPVI cleavage remains unknown. To address this, CRISPR/Cas9 knockout human cell lines were generated to show that Tspan15 and Tspan33 enact compensatory roles in GPVI cleavage, with Tspan15 bearing the more important role. To investigate this mechanism, a series of Tspan15 and GPVI mutant expression constructs were designed. The Tspan15 extracellular region was found to be critical in promoting GPVI cleavage, and appeared to achieve this by enabling ADAM10 to access the cleavage site at a particular distance above the membrane. These findings bear implications for the regulation of cleavage of other ADAM10 substrates, and provide new insights into post-translational regulation of the clinically relevant GPVI protein.},
  language  = {en}
}
@article{WolfahrtHermanScholzetal.2013,
  author    = {Wolfahrt, Sonja and Herman, Sandra and Scholz, Claus-J{\"u}rgen and Sauer, Georg and Deissler, Helmut},
  title     = {Identification of alternative transcripts of rat CD9 expressed by tumorigenic neural cell lines and in normal tissues},
  series = {Genetics and Molecular Biology},
  volume    = {36},
  journal   = {Genetics and Molecular Biology},
  number    = {2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131801},
  pages     = {276-281},
  year      = {2013},
  abstract  = {CD9 is the best-studied member of the tetraspanin family of transmembrane proteins. It is involved in various fundamental cellular processes and its altered expression is a characteristic of malignant cells of different origins. Despite numerous investigations confirming its fundamental role, the heterogeneity of CD9 or other tetraspanin proteins was considered only to be caused by posttranslational modification, rather than alternative splicing. Here we describe the first identification of CD9 transcript variants expressed by cell lines derived from fetal rat brain cells. Variant mRNA-B lacks a potential translation initiation codon in the alternative exon 1 and seems to be characteristic of the tumorigenic BT cell lines. In contrast, variant mRNA-C can be translated from a functional initiation codon located in its extended exon 2, and substantial amounts of this form detected in various tissues suggest a contribution to CD9 functions. From the alternative sequence of variant C, a different membrane topology ( 5 transmembrane domains) and a deviating spectrum of functions can be expected.},
  language  = {en}
}