12 research outputs found
Cell Invasion by Neisseria meningitidis Requires a Functional Interplay between the Focal Adhesion Kinase, Src and Cortactin
Entry of Neisseria meningitidis (the meningococcus) into human brain microvascular endothelial cells (HBMEC) is mediated by fibronectin or vitronectin bound to the surface protein Opc forming a bridge to the respective integrins. This interaction leads to cytoskeletal rearrangement and uptake of meningococci. In this study, we determined that the focal adhesion kinase (FAK), which directly associates with integrins, is involved in integrin-mediated internalization of N. meningitidis in HBMEC. Inhibition of FAK activity by the specific FAK inhibitor PF 573882 reduced Opc-mediated invasion of HBMEC more than 90%. Moreover, overexpression of FAK mutants that were either impaired in the kinase activity or were not capable of autophosphorylation or overexpression of the dominant-negative version of FAK (FRNK) blocked integrin-mediated internalization of N. meningitidis. Importantly, FAK-deficient fibroblasts were significantly less invaded by N. meningitidis. Furthermore, N. meningitidis induced tyrosine phosphorylation of several host proteins including the FAK/Src complex substrate cortactin. Inhibition of cortactin expression by siRNA silencing and mutation of critical amino acid residues within cortactin, that encompass Arp2/3 association and dynamin binding, significantly reduced meningococcal invasion into eukaryotic cells suggesting that both domains are critical for efficient uptake of N. meningitidis into eukaryotic cells. Together, these results indicate that N. meningitidis exploits the integrin signal pathway for its entry and that FAK mediates the transfer of signals from activated integrins to the cytoskeleton. A cooperative interplay between FAK, Src and cortactin then enables endocytosis of N. meningitidis into host cells
Labeled lines meet and talk: population coding of somatic sensations
The somatic sensory system responds to stimuli of distinct modalities, including touch, pain, itch, and temperature sensitivity. In the past century, great progress has been made in understanding the coding of these sensory modalities. From this work, two major features have emerged. First, there are specific neuronal circuits or labeled lines transmitting specific sensory information from the skin to the brain. Second, the generation of specific sensations often involves crosstalk among distinct labeled lines. These features suggest that population coding is the mechanism underlying somatic sensation
Relationships between the paradoxical painful and nonpainful sensations induced by a thermal grill
Thermoregulation and pain perception: Evidence for a homoeostatic (interoceptive) dimension of pain
Netrin-1-Induced Stem Cell Bioactivity Contributes to the Regeneration of Injured Tissues via the Lipid Raft-Dependent Integrin α6β4 Signaling Pathway
Subversion of phosphoinositide metabolism by intracellular bacterial pathogens
International audiencePhosphoinositides are short-lived lipids, whose production at specific membrane locations in the cell enables the tightly controlled recruitment or activation of diverse cellular effectors involved in processes such as cell motility or phagocytosis. Bacterial pathogens have evolved molecular mechanisms to subvert phosphoinositide metabolism in host cells, promoting (or blocking) their internalization into target tissues, and/or modifying the maturation fate of their proliferating compartments within the intracellular environment