Retracted Article: Spectrin-like domain 2 of DRP2 serves as a novel binding region for the NLS2 and 3 sub-domains of L-periaxin

Abstract

L-periaxin is an important scaffolding protein that is expressed in Schwann cells and lens fiber cells. In Schwann cells, loss or mutation of the PRX gene disrupts compact peripheral myelin and causes severe demyelination neuropathy. DRP2 is the only reported protein to interact with periaxin to form the Lperiaxin-DRP2-dystroglycan (PDG) complex, which can provide structural and signaling functions by linking the extracellular matrix to the Schwann cell cytoskeleton. In this report, the interaction between L-periaxin and DRP2 was further investigated by bimolecular fluorescence complementation (BiFC), GST pull-down, CO-IP, and fluorescence spectroscopy. Results demonstrated that spectrin-like domain 2 of DRP2 played a critical role in the complex of DRP2 and L-periaxin. Furthermore, the DRP2 spectrin-like domain 2 only interacted with the NLS2 and NLS3 sub-domains in L-periaxin. These data revealed a previously unknown binding model between DRP2 and L-periaxin. performed and analyzed the experiments results and wrote the paper, Yawei Shi conceived, designed, coordinated and modied the paper. All authors reviewed the results and approved the nal version of the manuscript. AbbreviationsDRP2 Dystroglycan-dystrophin-related proteins NLS Nuclear-localization-signal CMT Charcot-Marie-Tooth EPPD Ezrin-periplakin-periaxin-desmoyokin PDZ PSD-95/Discs Large/ZO-1 NES Nuclear export signal LMB Leptomycin B PNS Peripheral nervous system PDG L-periaxin-DRP2-dystroglycan EGFP Enhanced green uorescent protein YFP Yellow uorescent protein RFP Red uorescent protein GST Glutathione S-transferase BiFC Bimolecular uorescence complementation Co-IP Co-immunoprecipitation DAPI 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride FITC Fluorescein isothiocyanate This journal is

Retracted Article: Self-association of L-periaxin occursviaits acidic domain and NLS2/NLS3, and affects its trafficking in RSC96 cells

“…25 L-PRX on the cytomembrane interacts with DRP2 through its NLS domain. 16,18 The NLS domain plays a signicant role in the nuclear targeting and nuclearcytoplasmic trafficking of L-PRX. 18 Thus, this study investigated the relationship among the four different domains of L-PRX.…”

“…L-PRX could interact with DRP2 through its NLS domain. 16,18 A competitive co-immunoprecipitation experiment was performed to examine whether DRP2 affects L-PRX self-association. The western blot results showed the remarkably weakened interaction between the NLS and acidic domains of L-PRX when protein was competitively co-immunoprecipitated with DRP2 (Fig.…”

“…17 In addition, L-PRX could interact with S-PRX through the PDZ domain. 18 The NLS domain of L-PRX is basic, tripartite and composed of three synergistically acting signals, namely NLS1 (116-145 aa), NLS2 (145-176 aa) and NLS3 (177-196 aa). 14 This domain plays a key role in the nuclear targeting of L-PRX in embryonic Schwann cells and shuttling between the nucleus and cortical-signaling or adherence complexes.…”

Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease

“…The DRP2/dystroglycan complex is a major transmembrane assembly involved in the formation and stability of membrane appositions and Cajal bands in the Schwann cell abaxonal layer [13,200,201], and it is strictly found in appositions, whereas most of L-PRX is present in Cajal bands [13]. The interaction is thought to be mainly mediated by the DRP2 spectrin repeat domain, with possible involvement of the adjacent WW domain and NLS2/NLS3 in L-PRX ( Figure 8b) [13,202]. The NLS2/NLS3 region mediates a self-interaction within L-PRX by binding to the L-PRX acidic C terminus, although it is unclear whether the interaction is intramolecular or if two L-PRX molecules may interact [203].…”

Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease

“…The DRP2/dystroglycan complex is a major transmembrane assembly involved in the formation and stability of membrane appositions and Cajal bands in the Schwann cell abaxonal layer [13,196,197], and it is strictly found in appositions, whereas most of L-PRX is present in Cajal bands [13]. The interaction is thought to be mainly mediated by the DRP2 spectrin-repeat domain, with possible involvement of the adjacent WW domain, and NLS2/NLS3 in L-PRX ( Figure 7b) [13,198]. The NLS2/NLS3 region mediates a self-interaction within L-PRX by binding to its acidic C terminus, although it is unclear whether the interaction is intramolecular or if two L-PRX molecules may interact [199].…”