Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains. Issue 21 (23rd September 2013)

• Record Type: Journal Article
• Authors: Jian, Jinlong; Zhao, Shuai; Tian, Qingyun; Gonzalez-Gugel, Elena; Mundra, Jyoti Joshi; Uddin, Sardar MZ; Liu, Ben; Richbourgh, Brendon; Brunetti, Ryan; Liu, Chuan-ju
• Is Part Of: FEBS letters. Volume 587:Issue 21(2013)
• Page Start: 3428
• Page End: 3436
• Publication Date: 2013-09-23
• Subjects: PGRN -- progranulin -- TNFR -- tumor-necrotizing factor receptor -- CRD -- cysteine-rich domains -- BMDM -- bone marrow-derived macrophages -- SPR -- Surface plasmon resonance -- FTLD -- frontotemporal lobar degeneration -- Y2H -- yeast two-hybrid -- HRP -- horseradish peroxidase -- PGRN -- TNFα -- TNFR -- Sortilin -- Protein interaction; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.09.024
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : We previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al., Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN‐mediated anti‐inflammatory activity in various autoimmune diseases and conditions.