Fibronectin stimulates TRPV1 translocation in primary sensory neurons.
Extracellular matrix (ECM) molecules are highly variable in their composition and receptor recognition. Their ubiquitous expression profile has been linked to roles in cell growth, differentiation, and survival. Recent work has identified certain ECM molecules that serve as dynamic signal modulators, versus the more-recognized role of chronic modulation of signal transduction. In this study, we investigated the role that fibronectin (FN) plays in the dynamic modulation of transient receptor potential family V type 1 receptor (TRPV1) translocation to the plasma membrane in trigeminal ganglia (TG) sensory neurons. Confocal immunofluorescence analyses identify co-expression of the TRPV1 receptor with integrin subunits that bind FN. TG neurons cultured upon or treated with FN experienced a leftward shift in the EC(50) of capsaicin-stimulated neuropeptide release. This FN-induced increase in TRPV1 sensitivity to activation is coupled by an increase in plasma membrane expression of TRPV1, as well as an increase in tyrosine phosphorylation of TRPV1 in TG neurons. Furthermore, TG neurons cultured on FN demonstrated an increase in capsaicin-mediated Ca(2+) accumulation relative to neurons cultured on poly-D-lysine. Data presented from these studies indicate that FN stimulates tyrosine-phosphorylation-dependent translocation of the TRPV1 receptor to the plasma membrane, identifying FN as a critical component of the ECM capable of sensory neuron sensitization.
Jeske
Nathaniel A
NA
Department of Oral and Maxillofacial Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. jeske@uthscsa.edu
Patwardhan
Amol M
AM
Henry
Michael A
MA
Milam
Stephen B
SB
D000818:Animals; D001710:Biotin / Q000378:metabolism; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology*; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism*; D013268:Stimulation, Chemical; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology
D005353:Fibronectins; D016023:Integrins; D009479:Neuropeptides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014443:Tyrosine; D001710:Biotin; D019061:src-Family Kinases; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D002118:Calcium