Ttyh1, a Ca(2+)-binding protein localized to the endoplasmic reticulum, is required for early embryonic development.
Using comprehensive genetic studies on neuronal stem/progenitors cells through genome-wide screening with oligonucleotide arrays, we identified an endoplasmic reticulum (ER) -resident protein, Tweety homologue 1 (ttyh1). Ttyh1 encodes a glycosylated protein composed of five predicted transmembrane segments and a C-terminus that is enriched in negatively charged residues capable of Ca(2+) binding. Ttyh1-containing membranes changed to segmented tubuloreticular structures during mitosis, suggesting that the ER-containing Ttyh1 could be responsible for Ca(2+) sequestration and Ca(2+) concentration regulation during mitosis. Ttyh1 inactivation in mice resulted in early embryonic lethality before organization of the nervous system, revealing that ttyh1 is essential in murine embryonic development. Our findings indicate that Ttyh1 plays an indispensable role during mitosis in early embryogenesis, possibly by maintaining Ca(2+) homeostasis in the ER.
Kumada
Tomohiro
T
Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yamanaka
Yasunari
Y
Kitano
Ayumi
A
Shibata
Minoru
M
Awaya
Tomonari
T
Kato
Takeo
T
Okawa
Katsuya
K
Abe
Takaya
T
Oshima
Naoko
N
Nakahata
Tatsutoshi
T
Heike
Toshio
T
D000818:Animals; D002135:Calcium-Binding Proteins; D047108:Embryonic Development; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism; D055106:Genome-Wide Association Study; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D009474:Neurons / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000166:cytology
D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; C485951:Ttyh1 protein, mouse