Calnexin Delta 185-520 partially reverses the misprocessing of the Delta F508 cystic fibrosis transmembrane conductance regulator.
Abnormal retention of Delta F508 CFTR (cystic fibrosis transmembrane conductance regulator) in the endoplasmic reticulum is a major cause of cystic fibrosis (CF). We show that calnexin Delta 185-520 but not calnexin can partially reverse the mislocalization of Delta F508 CFTR. This 256-amino acid protein has neither the transmembrane domain nor the P domain of calnexin. Calnexin Delta 185-520 interacted with CFTR directly, and was secreted into the extracellular compartment over time. Forty-eight hours after transfection into CHO cells, calnexin Delta 185-520 increased the conversion of immature Delta F508 CFTR into mature Delta F508 CFTR. In immortalized human CF cell lines expressing Delta F508 CFTR, a halide efflux assay showed that calnexin Delta 185-520 partially restored CFTR function. These data indicate that calnexin Delta 185-520 may give a clue to develop the therapeutic way of cystic fibrosis with Delta F508 CFTR.
Okiyoneda
Tsukasa
T
Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Wada
Ikuo
I
Jono
Hirofumi
H
Shuto
Tsuyoshi
T
Yoshitake
Kazuhisa
K
Nakano
Nahoko
N
Nagayama
Shin-ichi
S
Harada
Kazutsune
K
Isohama
Yoichiro
Y
Miyata
Takeshi
T
Kai
Hirofumi
H
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D037281:Calnexin; D006224:Cricetinae; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000235:genetics*; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014132:Trachea / Q000502:physiology; D014162:Transfection
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D037281:Calnexin