Michael Patterson

Publications (2)11.44 Total impact

• Source

  Available from: PubMed Central

  Article: Signalling pathways underlying structural plasticity of dendritic spines.

  Michael Patterson, Ryohei Yasuda
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  ABSTRACT: Synaptic plasticity, or changes in synaptic strength, is thought to underlie learning and memory. Imaging studies, mainly in brain slices, have revealed that long-term synaptic plasticity of excitatory synapses in hippocampal neurons is coupled with structural plasticity of dendritic spines, which is thought to be essential for inducing and regulating functional plasticity. Using pharmacological and genetic manipulation, the signalling network underlying structural plasticity has been extensively studied. Furthermore, the recent advent of fluorescence resonance energy transfer (FRET) imaging techniques has provided a readout of the dynamics of signal transduction in dendritic spines undergoing structural plasticity. These studies reveal the signalling pathways relaying Ca(2+) to the functional and structural plasticity of dendritic spines.
  British Journal of Pharmacology 03/2011; 163(8):1626-38. · 4.41 Impact Factor
• Source

  Available from: PubMed Central

  Article: TRPV4-mediated calcium influx into human bronchial epithelia upon exposure to diesel exhaust particles.

  Jinju Li, Patrick Kanju, Michael Patterson, Wei-Leong Chew, Seung-Hyun Cho, Ian Gilmour, Tim Oliver, Ryohei Yasuda, Andrew Ghio, Sidney A Simon, Wolfgang Liedtke
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  ABSTRACT: Human respiratory epithelia function in airway mucociliary clearance and barrier function and have recently been implicated in sensory functions. We investigated a link between chronic obstructive pulmonary disease (COPD) pathogenesis and molecular mechanisms underlying Ca2+ influx into human airway epithelia elicited by diesel exhaust particles (DEP). Using primary cultures of human respiratory epithelial (HRE) cells, we determined that these cells possess proteolytic signaling machinery, whereby proteinase-activated receptor-2 (PAR-2) activates Ca2+-permeable TRPV4, which leads to activation of human respiratory disease-enhancing matrix metalloproteinase-1 (MMP-1), a signaling cascade initiated by diesel exhaust particles (DEP), a globally relevant air pollutant. Moreover, we observed ciliary expression of PAR-2, TRPV4, and phospholipase-Cβ3 in human airway epithelia and their DEP-enhanced protein-protein complex formation. We also found that the chronic obstructive pulmonary disease (COPD)-predisposing TRPV4P19S variant enhances Ca2+ influx and MMP 1 activation, providing mechanistic linkage between man-made air pollution and human airway disease. DEP evoked protracted Ca2+ influx via TRPV4, enhanced by the COPD-predisposing human genetic polymorphism TRPV4P19S. This mechanism reprograms maladaptive inflammatory and extracellular-matrix-remodeling responses in human airways. The novel concept of air pollution-responsive ciliary signal transduction from PAR-2 to TRPV4 in human respiratory epithelia will accelerate rationally targeted therapies, possibly via the inhalatory route.
  Environmental Health Perspectives 01/2011; 119(6):784-93. · 7.04 Impact Factor