| Radixin, a key member of the ERM (ezrin-radixin-moesin) protein family that links plasma membranes to the actin cytoskeleton, regulates cortical architecture, cell polarity, and motility through conformational activation at its C-terminal threonine residue. In its dormant state, intramolecular masking between the N-terminal FERM domain and C-terminal actin-binding tail maintains cytosolic sequestration, but phosphorylation at Thr564 by Rho-associated kinase or PKC disrupts this clamp, unmasking membrane-binding sites for CD44/ICAMs and F-actin tails to stabilize microvilli, lamellipodia, and tight junctions. Activated radixin scaffolds MRP-2 trafficking to apical canaliculi in polarized hepatocytes via ezrin/radixin/moesin phosphorylation cycling that responds to phosphatase inhibition or metabolic stress, while Gα13/RhoA signaling engages radixin's C-terminus to stimulate Rac1 and CaMKII, driving serum response element transcription and cytoskeletal remodeling. In colon epithelia, radixin overexpression hyperactivates Rac1-ERK cascades that boost MMP-7 secretion for basement membrane invasion, whereas Thr564 mutants reveal non-phosphorylatable forms that preserve polarity but abolish MRP-2 function, positioning radixin as the dominant ERM paralog for dissecting vectorial transport. Radixin maintains bile canalicular integrity and hepatocyte plate architecture, with conditional ablation disrupting Mrp-2 localization and organic anion efflux critical for xenobiotic clearance. Upregulation correlates with colorectal cancer progression through enhanced invadopodia while lung adenocarcinoma shows paradoxical downregulation suggesting context-dependent suppression; Akt2-mediated Thr564 phosphorylation links PI3K signaling to polarity loss. |
Lane 1: Hela, Lane 2: NIH/3T3, Lane 3: COS, Lane 4: C6
