Calumin, a novel Ca2+-binding transmembrane protein on the endoplasmic reticulum.
We have identified a novel endoplasmic reticulum (ER)-resident protein, named "calumin", which is expressed in various tissues. This protein has a molecular mass of approximately 60 kDa and is composed of an ER-luminal domain rich in acidic residues, a single transmembrane segment, and a large cytoplasmic domain. Biochemical experiments demonstrated that the amino-terminal luminal domain is capable of binding Ca2+ with a high capacity and moderate affinity. In embryonic fibroblasts derived from calumin-knockout mice exhibiting embryonic and neonatal lethality, fluorometric Ca2+ imaging detected insufficient Ca2+ contents in intracellular stores and attenuated store-operated Ca2+ entry. Moreover, the mutant fibroblasts were highly sensitive to cell death induced by ER stress. These observations suggest that calumin plays an essential role in ER Ca2+ handling and is also implicated in signaling from the ER, which is closely associated with cell-fate decision.
Zhang
Miao
M
Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Yamazaki
Tetsuo
T
Yazawa
Masayuki
M
Treves
Susan
S
Nishi
Miyuki
M
Murai
Machiko
M
Shibata
Eisuke
E
Zorzato
Francesco
F
Takeshima
Hiroshi
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000502:physiology*; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000737:chemistry*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008970:Molecular Weight; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D014415:Tunicamycin; D019284:Thapsigargin; D002118:Calcium