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Ttyh1, a Ca 2+ ‐binding protein localized to the endoplasmic reticulum, is required for early embryonic development
Author(s) -
Kumada Tomohiro,
Yamanaka Yasunari,
Kitano Ayumi,
Shibata Minoru,
Awaya Tomonari,
Kato Takeo,
Okawa Katsuya,
Abe Takaya,
Oshima Naoko,
Nakahata Tatsutoshi,
Heike Toshio
Publication year - 2010
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22348
Subject(s) - endoplasmic reticulum , biology , mitosis , microbiology and biotechnology , embryonic stem cell , embryogenesis , transmembrane protein , gene , embryo , biochemistry , receptor
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. Developmental Dynamics 239:2233–2245, 2010. © 2010 Wiley‐Liss, Inc.