Cellular micro-environments reveal defective mechanosensing responses and elevated YAP signaling in LMNA-mutated muscle precursors

• DOI: 10.1242/jcs.144907
• Publication Date: 2014-05-08T03:00:43Z
• Authors: Anne T Bertrand; Simindokht Ziaei; Camille Ehret; Hélène Duchemin; Kamel Mamchaoui; Anne Bigot; Michèle Mayer; Susana Quijano-Roy; Isabelle Desguerre; Jeanne Lainé; Rabah Ben Yaou; Gisèle Bonne; Catherine Coirault
• Keywords: LMNA

The mechanisms underlying cell response to mechanical forces are critical for muscle development and functionality. We aim determine whether mutations of the LMNA gene causing congenital muscular dystrophy impair ability precursors sense tissue stiffness respond challenge. found that LMNA-mutated myoblasts (LMNA) embedded in soft matrix did not align along gel axis whereas control did. were unable tune their cytoskeletal tension as attested by inappropriate cell-matrix adhesion sites versus rigid substrates or after Importantly, 2D and/or static 3D conditions, demonstrated enhanced activation Yes-Associated Protein (YAP) signaling pathway was paradoxically reduced cyclic stretch. SiRNA-mediated downregulation YAP actin stress fibers myoblasts. This is first demonstration human with have mechanosensing defects through a YAP-dependent pathway. In addition, our data emphasize crucial role biophysical attributes cellular microenvironment pathways lamin A/C mutated