Integrins regulate opioid receptor signaling in trigeminal ganglion neurons

Autor: Stephen B. Milam, Kenneth M. Hargreaves, William P. Clarke, Kelly A. Berg, Gustavo Zardeneta
Rok vydání: 2007
Předmět:
Zdroj: Neuroscience. 144:889-897
ISSN: 0306-4522
DOI: 10.1016/j.neuroscience.2006.10.033
Popis: Cells interact with the extracellular matrix via heterodimeric (αβ) transmembrane receptors, termed integrins (Giancotti and Rouslahti, 1999). Integrins are expressed by virtually every cell type and are known to be involved in the regulation of several vital cell functions, including adhesion, migration, proliferation, and differentiation (Milam et al., 1991, Hynes, 1992, Curley et al., 1999, Giancotti and Rouslahti, 1999, Schlaepfer et al., 1999, Coppolino and Dedhar, 2000, Bouvard et al., 2001, Zamir and Geiger, 2001, Alenghat and Ingber, 2002, Martin et al., 2002, Miranti and Brugge, 2002). Eighteen α and eight β subunits have been identified forming at least 24 different αβ integrins (van der Flier and Sonnenberg, 2001, Miranti and Brugge, 2002). However, splice variants of integrins are known to exist that potentially increase the functional diversity of these important molecules (Melker and Sonnenberg, 1999). Integrins composed of α4, α5, α8, αIIb, or αv subunits (ten of the known 24 integrins contain one of these α subunits) bind to molecules containing an arginine-glycine-aspartate (RGD) sequence (van der Flier and Sonnenberg, 2001). This RGD peptide sequence is exposed in intact fibronectin and vitronectin, and is contained as cryptic, or inaccessible, primary structure in some intact laminins and collagens. Integrins that are bound to domains on the extracellular matrix (or to RGD peptides bound to a solid substrate) initiate intracellular signals (i.e., “outside-in” signaling) (Coppolino and Dedhar, 2000). The application of soluble RGD-peptides to neuronal cultures evoked a rapid and substantial increase in the spontaneous discharges of parietal motor neurons (Wildering et al., 2002). Furthermore, administration of soluble RGD peptides, but not the inactive control peptide sequence (i.e., DGR), enhanced high-voltage-activated Ca++ currents in these neurons. Application of RGD peptides, or anti-integrin antibodies, but not inactive control peptides, have also been shown to block N-methyl-D-aspartate (NMDA)-mediated excitatory postsynaptic currents in hippocampal neurons (Chavis and Westbrook, 2001) suggesting that RGD-binding integrins are important in neurotransmission. With respect to their potential significance in opioid receptor signaling, it is important to note that integrins may modulate G-protein coupled receptor (GPCR) signaling in the CNS (McPhee et al., 1998) as well as in other tissues (Della Rocca et al., 1999, Litvak et al., 2000, Short et al., 2000, Slack and Siniaia, 2005). In the present study, we addressed two major issues related to integrin regulation of sensory neurons. First, we characterized the expression pattern of integrin in sensory neurons, specifically trigeminal ganglion neurons. Second, we tested the hypothesis that the RGD class of integrins regulates the signaling of the GPCR mu opioid receptor (MOR) in trigeminal ganglion neurons.
Databáze: OpenAIRE
Externí odkaz: