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Metropolitan Government of Nashville-Davidson (balance), TN, United States

Jean L.,Center for Research on Human Development | Majumdar D.,Center for Research on Human Development | Shi M.,Center for Research on Human Development | Hinkle L.E.,Center for Research on Human Development | And 8 more authors.
Journal of Cell Science | Year: 2013

Summary Non-muscle myosin II (MyoII) contractility is central to the regulation of numerous cellular processes, including migration. Rho is a well-characterized modulator of actomyosin contractility, but the function of other GTPases, such as Rac, in regulating contractility is currently not well understood. Here, we show that activation of Rac by the guanine nucleotide exchange factor Asef2 (also known as SPATA13) impairs migration on type I collagen through a MyoII-dependent mechanism that enhances contractility. Knockdown of endogenous Rac or treatment of cells with a Rac-specific inhibitor decreases the amount of active MyoII, as determined by serine 19 (S19) phosphorylation, and negates the Asef2-promoted increase in contractility. Moreover, treatment of cells with blebbistatin, which inhibits MyoII activity, abolishes the Asef2-mediated effect on migration. In addition, Asef2 slows the turnover of adhesions in protrusive regions of cells by promoting large mature adhesions, which has been linked to actomyosin contractility, with increased amounts of active β1 integrin. Hence, our data reveal a new role for Rac activation, promoted by Asef2, in modulating actomyosin contractility, which is important for regulating cell migration and adhesion dynamics. © 2013. Source

Qiu S.,Center for Research on Human Development | Qiu S.,Vanderbilt University | Champagne D.L.,Leiden Amsterdam Center for Drug Research | Peters M.,University of South Florida | And 6 more authors.
Biological Psychiatry | Year: 2010

Background: The limbic system-associated membrane protein (LAMP) promotes development of neurons of limbic origin. We have previously shown that genetic deletion of LAMP results in heightened reactivity to novelty and reduced anxiety-like behaviors in mice. Here, we demonstrate a critical role of LAMP in hippocampal-dependent synaptic physiology and behavior. Methods: We tested spatial memory performance, hippocampal synaptic plasticity, and stress-related modalities in Lsamp-/- mice and their littermate control mice. Results: Lsamp-/- mice exhibit a pronounced deficit in spatial memory acquisition and poorly sustained CA1 long-term potentiation. We found reduced expression of mineralocorticoid receptor (MR) transcripts in the hippocampus and reduction in the corticosterone-induced, MR-mediated nongenomic modulatory effects on CA1 synaptic transmission. Importantly, the impaired long-term potentiation in Lsamp-/- mice can be rescued by stress-like levels of corticosterone in a MR-dependent manner. Conclusions: Our study reveals a novel functional relationship between a cell adhesion molecule enriched in developing limbic circuits, glucocorticoid receptors, and cognitive functioning. © 2010 Society of Biological Psychiatry. Source

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