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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 \u03bcM, 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 Ca<jats:sup>2+<\/jats:sup>and PKC\u03b1 inhibition (Go6976). In vitro assays revealed that PKC\u03b1 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 Ca<jats:sup>2+<\/jats:sup>and PKC\u03b1-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.<\/jats:p>","DOI":"10.1152\/ajpgi.90362.2008","type":"journal-article","created":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T01:19:03Z","timestamp":1217553543000},"page":"G700-G708","source":"Crossref","is-referenced-by-count":10,"title":["Serotonin modifies cytoskeleton and brush-border membrane architecture in human intestinal epithelial cells"],"prefix":"10.1152","volume":"295","author":[{"given":"Ravinder K.","family":"Gill","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerrold R.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seema","family":"Saksena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waddah A.","family":"Alrefai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nitika","family":"Pant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Esmaili","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alka","family":"Dwivedi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishnamurthy","family":"Ramaswamy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep K.","family":"Dudeja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608557200"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1051\/rnd:19890405"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1988.tb08404.x"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500505200"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1136\/gut.18.11.882"},{"key":"R6","unstructured":"Chen ZZ, McGuire JC, Leach KL, Cambier JC.Transmembrane signaling through B cell MHC class II molecules: anti-Ia antibodies induce protein kinase C translocation to the nuclear fraction.J Immunol138: 2345\u20132352, 1987."},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716514"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29218"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.01.059"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2005.10.035"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/0959-440X(95)80103-0"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1007\/BF01297056"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1038\/nature01020"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01122"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1007\/s004180050151"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.02.011"},{"key":"R17","doi-asserted-by":"crossref","unstructured":"Halsey DL, Girard PR, Kuo JF, Blackshear PJ.Protein kinase C in fibroblasts. 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