Serotonin modifies cytoskeleton and brush-border membrane architecture in human intestinal epithelial cells Export

@article{citeulike:3392090, abstract = {Serotonin or 5-hydroxytryptamine (5-HT) influences numerous functions in the gastrointestinal tract. We previously demonstrated that 5-HT treatment of Caco-2 cells inhibited Na+/H+ exchangers (NHE) and Cl-/OH- exchange activities via distinct signaling mechanisms. Since regulation of several ion transporters such as NHE3 is influenced by intact cytoskeleton, we hypothesized that 5-HT modifies actin cytoskeleton and/or brush-border membrane architecture via involvement of signaling pathways. Ultrastructural analysis showed that 5-HT (0.1 {micro}M, 1 h) treatment of Caco-2 cells caused the apical membrane to assume a convex dome shape that was associated with shortening of microvilli. To examine whether these cellular architecture changes are cytoskeleton driven, we analyzed actin cytoskeleton by fluorescence microscopy. 5-HT induced basal stress fibers with prominent cortical actin filaments via 5-HT3 and 5-HT4 receptor subtypes. This induction was partially attenuated by chelation of intracellular Ca2+ and PKC{alpha} inhibition (Go6976). In vitro assays revealed that PKC{alpha} interacted with actin and this association was increased by 5-HT. Our data provide novel evidence that 5-HT-induced signaling via 5-HT3/4 receptor subtypes to cause Ca2+ and PKC{alpha}-dependent regulation of actin cytoskeleton may play an important role in modulation of ion transporters that contribute to pathophysiology of diarrheal conditions associated with elevated levels of 5-HT. 10.1152/ajpgi.90362.2008}, author = {Gill, Ravinder K. and Shen, Le and Turner, Jerrold R. and Saksena, Seema and Alrefai, Waddah A. and Pant, Nitika and Esmaili, Ali and Dwivedi, Alka and Ramaswamy, Krishnamurthy and Dudeja, Pradeep K.}, citeulike-article-id = {3392090}, citeulike-linkout-0 = {http://dx.doi.org/10.1152/ajpgi.90362.2008}, citeulike-linkout-1 = {http://ajpgi.physiology.org/cgi/content/abstract/295/4/G700}, day = {1}, doi = {10.1152/ajpgi.90362.2008}, journal = {Am J Physiol Gastrointest Liver Physiol}, keywords = {5-ht, actin, cytoskeleton, ion\_transporter, microvilli, serotonin, stress\_fibers}, month = {October}, number = {4}, pages = {G700--708}, posted-at = {2008-10-10 02:10:17}, priority = {3}, title = {Serotonin modifies cytoskeleton and brush-border membrane architecture in human intestinal epithelial cells}, url = {http://dx.doi.org/10.1152/ajpgi.90362.2008}, volume = {295}, year = {2008} }

TY - JOUR ID - citeulike:3392090 L3 - citeulike-article-id:3392090 N2 - Serotonin or 5-hydroxytryptamine (5-HT) influences numerous functions in the gastrointestinal tract. We previously demonstrated that 5-HT treatment of Caco-2 cells inhibited Na+/H+ exchangers (NHE) and Cl-/OH- exchange activities via distinct signaling mechanisms. Since regulation of several ion transporters such as NHE3 is influenced by intact cytoskeleton, we hypothesized that 5-HT modifies actin cytoskeleton and/or brush-border membrane architecture via involvement of signaling pathways. Ultrastructural analysis showed that 5-HT (0.1 {micro}M, 1 h) treatment of Caco-2 cells caused the apical membrane to assume a convex dome shape that was associated with shortening of microvilli. To examine whether these cellular architecture changes are cytoskeleton driven, we analyzed actin cytoskeleton by fluorescence microscopy. 5-HT induced basal stress fibers with prominent cortical actin filaments via 5-HT3 and 5-HT4 receptor subtypes. This induction was partially attenuated by chelation of intracellular Ca2+ and PKC{alpha} inhibition (Go6976). In vitro assays revealed that PKC{alpha} interacted with actin and this association was increased by 5-HT. Our data provide novel evidence that 5-HT-induced signaling via 5-HT3/4 receptor subtypes to cause Ca2+ and PKC{alpha}-dependent regulation of actin cytoskeleton may play an important role in modulation of ion transporters that contribute to pathophysiology of diarrheal conditions associated with elevated levels of 5-HT. 10.1152/ajpgi.90362.2008 IS - 4 JF - Am J Physiol Gastrointest Liver Physiol EP - 708 TI - Serotonin modifies cytoskeleton and brush-border membrane architecture in human intestinal epithelial cells VL - 295 SP - G700 KW - 5-ht KW - actin KW - cytoskeleton KW - ion_transporter KW - microvilli KW - serotonin KW - stress_fibers AU - Gill, Ravinder AU - Shen, Le AU - Turner, Jerrold AU - Saksena, Seema AU - Alrefai, Waddah AU - Pant, Nitika AU - Esmaili, Ali AU - Dwivedi, Alka AU - Ramaswamy, Krishnamurthy AU - Dudeja, Pradeep PY - 2008/10/01/ UR - http://dx.doi.org/10.1152/ajpgi.90362.2008 ER -