Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane.
Klotho mutant mice exhibit a set of phenotypes resembling human ageing. Although the function of Klotho remains unclear, mediation of its pleiotropic functions by putative humoral factor(s) has been presumed. Newly established antibodies against Klotho allowed the detection of secreted Klotho, a candidate for the putative humoral factor, in sera and cerebrospinal fluid. Surprisingly the secreted Klotho was 130 kDa, in contrast to the 70 kDa predicted form from klotho gene transcripts. The secreted as well as the membrane-bound Klotho proteins were suggested to form oligomerized complex. These results delineate post-translation processing of Klotho and possible regulatory mechanisms for secretion of Klotho in vivo.
Imura
Akihiro
A
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto 606-8501, Japan.
Iwano
Akiko
A
Tohyama
Osamu
O
Tsuji
Yoshihito
Y
Nozaki
Kazuhiko
K
Hashimoto
Nobuo
N
Fujimori
Toshihiko
T
Nabeshima
Yo-Ichi
Y
D017398:Alternative Splicing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015153:Blotting, Western; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D002845:Chromatography; D002850:Chromatography, Gel; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D005966:Glucuronidase; D006031:Glycosylation; D000090265:Klotho Proteins; D008565:Membrane Proteins / Q000097:blood* / Q000134:cerebrospinal fluid*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D012333:RNA, Messenger; D005966:Glucuronidase; D000090265:Klotho Proteins