title: Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D.
abstract: The sensing of physical force, mechanosensation, underlies two of five human senses-touch and hearing. How transduction of force in a membrane occurs remains unclear. We asked if a biological membrane could employ kinetic energy to transduce a signal absent tension. Here we show that lipid rafts are dynamic compartments that inactivate the signalling enzyme phospholipase D2 (PLD2) by sequestering the enzyme from its substrate. Mechanical disruption of the lipid rafts activates PLD2 by mixing the enzyme with its substrate to produce the signalling lipid phosphatidic acid (PA). We calculate a latency time of <650 μs for PLD activation by mixing. Our results establish a fast, non-tension mechanism for mechanotransduction where disruption of ordered lipids initiates a mechanosensitive signal for cell growth through mechanical mixing.
authors.affiliation: Departments of Molecular Therapeutics and Neuroscience, The Scripps Research Institute, Scripps, Florida 33458, USA.
authors.forename: E Nicholas
authors.initials: EN
authors.lastname: Petersen
authors.affiliation: Departments of Molecular Therapeutics and Neuroscience, The Scripps Research Institute, Scripps, Florida 33458, USA.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Chung
authors.affiliation: Departments of Molecular Therapeutics and Neuroscience, The Scripps Research Institute, Scripps, Florida 33458, USA.
authors.forename: Arman
authors.initials: A
authors.lastname: Nayebosadri
authors.affiliation: Departments of Molecular Therapeutics and Neuroscience, The Scripps Research Institute, Scripps, Florida 33458, USA.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Hansen
mesh_terms: D000818:Animals; D002460:Cell Line; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D040542:Mechanotransduction, Cellular; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D049452:Green Fluorescent Proteins; C105606:phospholipase D2; D010739:Phospholipase D