title: The role of the interaction of the vinculin proline-rich linker region with vinexin α in sensing the stiffness of the extracellular matrix.
abstract: Although extracellular matrix (ECM) stiffness is an important aspect of the extracellular microenvironment and is known to direct the lineage specification of stem cells and affect cancer progression, the molecular mechanisms that sense ECM stiffness have not yet been elucidated. In this study, we show that the proline-rich linker (PRL) region of vinculin and the PRL-region-binding protein vinexin are involved in sensing the stiffness of ECM substrates. A rigid substrate increases the level of cytoskeleton-associated vinculin, and the fraction of vinculin stably localizing at focal adhesions (FAs) is larger on rigid ECM than on soft ECM. Mutations in the PRL region or the depletion of vinexin expression impair these responses to ECM stiffness. Furthermore, vinexin depletion impairs the stiffness-dependent regulation of cell migration. These results suggest that the interaction of the PRL region of vinculin with vinexin α plays a crucial role in sensing ECM stiffness and in mechanotransduction.
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuyama
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
authors.forename: Susan W
authors.initials: SW
authors.lastname: Craig
authors.forename: Ichiro
authors.initials: I
authors.lastname: Harada
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kioka
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002942:Circular Dichroism; D005109:Extracellular Matrix / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D047468:Immunoprecipitation; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing
chemical_list: D009124:Muscle Proteins; C117452:Sorbs3 protein, mouse; D048868:Adaptor Proteins, Signal Transducing
keywords: Extracellular matrix; Mechanotransduction; Stiffness; Vinculin