UNLABELLED: Biological functions of receptor tyrosine kinase-like orphan receptor 1 (ROR1) remain to be elucidated due to the lack of identified genuine ligands. Previously, transiently expressed ROR1 was unexpectedly found to exhibit nuclear localization, the functions of which are unknown. MATERIALS AND METHODS: We constructed nuclear-homing peptidyl-prolyl cis-trans isomerases (FKBP) domain fusion ROR1-expressing cells and used a synthetic dimerizer to specifically activate FKBP-fused ROR1 proteins for subsequent functional characterization. RESULTS: Activation of nuclear-homing ROR1 by treating cells with AP20187 dimerizer led to significant increase in actin stress fibers and increased cellular migration. Following gene expression microarray analysis, we demonstrated that activated ROR1 affects several genes involved in the regulation of the actin cytoskeleton (radixin (RDX), ezrin (EZR), son of sevenless homolog 2 (SOS2) and caldesmon 1 (CALD1)). CONCLUSION: Our data indicate that nuclear-localized ROR1 may play an important role in cell migration and cytoskeleton remodeling. This might explain the critical roles of ROR1 in neuron development.
UNLABELLED: Biological functions of receptor tyrosine kinase-like orphan receptor 1 (ROR1) remain to be elucidated due to the lack of identified genuine ligands. Previously, transiently expressed ROR1 was unexpectedly found to exhibit nuclear localization, the functions of which are unknown. MATERIALS AND METHODS: We constructed nuclear-homing peptidyl-prolyl cis-trans isomerases (FKBP) domain fusion ROR1-expressing cells and used a synthetic dimerizer to specifically activate FKBP-fused ROR1 proteins for subsequent functional characterization. RESULTS: Activation of nuclear-homing ROR1 by treating cells with AP20187 dimerizer led to significant increase in actin stress fibers and increased cellular migration. Following gene expression microarray analysis, we demonstrated that activated ROR1 affects several genes involved in the regulation of the actin cytoskeleton (radixin (RDX), ezrin (EZR), son of sevenless homolog 2 (SOS2) and caldesmon 1 (CALD1)). CONCLUSION: Our data indicate that nuclear-localized ROR1 may play an important role in cell migration and cytoskeleton remodeling. This might explain the critical roles of ROR1 in neuron development.
Authors: Sara E Konopelski Snavely; Michael W Susman; Ryan C Kunz; Jia Tan; Srisathya Srinivasan; Michael D Cohen; Kyoko Okada; Helen Lamb; Shannon S Choi; Edith P Karuna; Michael K Scales; Steven P Gygi; Michael Eldon Greenberg; Hsin-Yi Henry Ho Journal: Proc Natl Acad Sci U S A Date: 2021-06-22 Impact factor: 11.205
Authors: Tara K Sigdel; Lorelei D Shoemaker; Rong Chen; Li Li; Atul J Butte; Minnie M Sarwal; Gary K Steinberg Journal: Orphanet J Rare Dis Date: 2013-03-21 Impact factor: 4.123
Authors: M Hojjat-Farsangi; A H Daneshmanesh; A S Khan; J Shetye; F Mozaffari; P Kharaziha; L-S Rathje; P Kokhaei; L Hansson; J Vågberg; S Byström; E Olsson; C Löfberg; C Norström; J Schultz; M Norin; T Olin; A Österborg; H Mellstedt; A Moshfegh Journal: Leukemia Date: 2018-03-27 Impact factor: 11.528