title: Integrin-mediated membrane blebbing is dependent on sodium-proton exchanger 1 and sodium-calcium exchanger 1 activity.
abstract: Integrin signaling and membrane blebbing modulate cell adhesion, spreading, and migration. However, the relationship between integrin signaling and membrane blebbing is unclear. Here, we show that an integrin-ligand interaction induces both membrane blebbing and changes in membrane permeability. Sodium-proton exchanger 1 (NHE1) and sodium-calcium exchanger 1 (NCX1) are membrane proteins located on the bleb membrane. Inhibition of NHE1 disrupts membrane blebbing and decreases changes in membrane permeability. However, inhibition of NCX1 enhances cell blebbing; cells become swollen because of NHE1 induced intracellular sodium accumulation. Our study found that NHE1 induced sodium influx is a driving force for membrane bleb growth, while sodium efflux (and calcium influx) induced by NCX1 in a reverse mode results in membrane bleb retraction. Together, these findings reveal a novel function for NHE1 and NCX1 in membrane blebbing and permeability, and establish a link between membrane blebbing and integrin signaling.
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.; Department of Biomedical Sciences, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Yi
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Physiology, National Yang-Ming University, Taipei 112, Taiwan, R.O.C., and.
authors.forename: Tien-Shen
authors.initials: TS
authors.lastname: Lew
authors.affiliation: Department of Physiology, National Taiwan University, Taipei 100, Taiwan, R.O.C.
authors.forename: Chih-Yung
authors.initials: CY
authors.lastname: Tang
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Wei-Lien
authors.initials: WL
authors.lastname: Tseng
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Tseng
authors.affiliation: Department of Biomedical Sciences, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan, R.O.C.; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.. Electronic address: losj@mail.cgu.edu.tw.
authors.forename: Szecheng J
authors.initials: SJ
authors.lastname: Lo
mesh_terms: D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology; D021961:Cell Membrane Structures / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D016023:Integrins; C490998:SLC9A1 protein, human; D019831:Sodium-Calcium Exchanger; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; C110374:sodium-calcium exchanger 1; D012964:Sodium; D002118:Calcium