Posttranslational proteolytic processing of Leda-1/Pianp involves cleavage by MMPs, ADAM10/17 and gamma-secretase

作者：Biswas Siladitta; Adrian Monica; Weber Jochen; Evdokimov Konstantin; Winkler Manuel; Geraud Cyrill^*

来源：Biochemical and Biophysical Research Communications, 2016, 477(4): 661-666.

DOI：10.1016/j.bbrc.2016.06.116

• Gamma secretase
• Proteolysis
• ADAM
• Immune regulation
• Nervous system

Leda-1/Pianp is a type I transmembrane protein expressed by CNS cells, murine melanoma cell line B16F10 and rat liver sinusoidal endothelial cells. The early steps of posttranslational modifications of Leda-1/Pianp have been described to include glycosylation and processing by proprotein convertases. Here, we comprehensively characterized the subsequent steps of proteolytic processing of Leda-1/Pianp. For this purpose specific protease inhibitors and cell lines deficient in PS1, PS2, PS1/PS2 and ADAM10/17 were deployed. Leda-1/Pianp was cleaved at numerous cleavage sites within the N-terminal extracellular domain. The sheddases involved included MMPs and ADAM10/17. Ectodomain shedding yielded C-terminal fragments (CTF) of -15 kDa. The CTF was further processed by the gamma (gamma)-secretase complex to generate the intracellular domain (ICD) of similar to 10 kDa. Although PS1 was the dominant intramembrane protease, PS2 was also able to cleave Leda-1/Pianp in the absence of PS1. Thus, Leda-1/Pianp is constitutively processed by proprotein convertases, sheddases including MMPs and ADAM10/17 and intramembrane protease gamma-secretase.

• 出版日期2016-9-2