000K  utf8
1100  $c2022
1500  eng
2050  urn:nbn:de:gbv:8:3-2024-00187-4
2051  10.3390/membranes12020123
3000  Leitzke, Sinje
3010  Ahrens, Björn
3010  Bhakdi, Sucharit
3010  Kunzelmann, Karl
3010  Reiss, Karina
3010  Schreiber, Rainer
3010  Seidel, Jana
3010  Sperrhacke, Maria
4000  Influence of Anoctamin-4 and -9 on ADAM10 and ADAM17 Sheddase Function$hMDPI AG  [Leitzke, Sinje]
4030  $nMDPI AG
4209  Ca2+-activated Cl- channels (TMEM16, also known as anoctamins) perform important functions in cell physiology, including modulation of cell proliferation and cancer growth. Many members, including TMEM16F/ANO6, additionally act as Ca2+-activated phospholipid scramblases. We recently presented evidence that ANO6-dependent surface exposure of phosphatidylserine (PS) is pivotal for the disintegrin-like metalloproteases ADAM10 and ADAM17 to exert their sheddase function. Here, we compared the influence of seven ANO family members (ANO1, 4, 5, 6, 7, 9, and 10) on ADAM sheddase activity. Similar to ANO6, overexpression of ANO4 and ANO9 led to increased release of ADAM10 and ADAM17 substrates, such as betacellulin, TGFα, and amphiregulin (AREG), upon ionophore stimulation in HEK cells. Inhibitor experiments indicated that ANO4/ANO9-mediated enhancement of TGFα-cleavage broadened the spectrum of participating metalloproteinases. Annexin V-staining demonstrated increased externalisation of PS in ANO4/ANO9-overexpressing cells. Competition experiments with the soluble PS-headgroup phosphorylserine indicated that the ANO4/ANO9 effects were due to increased PS exposure. Overexpression of ANO4 or ANO9 in human cervical cancer cells (HeLa), enhanced constitutive shedding of the growth factor AREG and increased cell proliferation. We conclude that ANO4 and ANO9, by virtue of their scramblase activity, may play a role as important regulators of ADAM-dependent cellular functions.
4950  https://doi.org/10.3390/membranes12020123$xR$3Volltext$534
4950  https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2024-00187-4$xR$3Volltext$534
4961  https://macau.uni-kiel.de/receive/macau_mods_00004468
5051  610
5550  Adam10
5550  Adam17
5550  Anoctamins
5550  Phosphatidylserine
5550  Scramblases
5550  Shedding