Mice doubly-deficient in the Arf GAPs SMAP1 and SMAP2 exhibit embryonic lethality

• Published in: FEBS letters Vol. 589; no. 19; pp. 2754 - 2762
• Main Authors: Sumiyoshi, Mami, Masuda, Narumi, Tanuma, Nobuhiro, Ogoh, Honami, Imai, Eri, Otsuka, Mizuki, Hayakawa, Natsuki, Ohno, Kinuyo, Matsui, Yasuhisa, Hara, Kanae, Gotoh, Risa, Suzuki, Mai, Rai, Shinya, Tanaka, Hirokazu, Matsumura, Itaru, Shima, Hiroshi, Watanabe, Toshio
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 14.09.2015
• Subjects: Animals; Apoptosis; Arf GAP; Cell Line; Embryo, Mammalian - cytology; Embryo, Mammalian - embryology; Embryogenesis; Embryonic Development; Endocytosis; Genetic interaction; Humans; Membrane Proteins - deficiency; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Protein Transport; Sequence Deletion; SMAP1; SMAP2; Transferrin - metabolism; Arf GAP; Embryogenesis; Genetic interaction; SMAP2; SMAP1
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2015.07.050

•The Arf GAPs SMAP1 and 2 reportedly exert distinct activities in membrane trafficking.•SMAP1 and 2 have not been shown to function embryonically.•Loss of SMAP1 and SMAP2 promotes embryonic lethality.•Mice doubly-deficient in the SMAP1 and SMAP2 promoted apoptosis in E7.5 embryos.•SMAP1 and 2 proteins complement each other to support proper embryonic development. In mammals, the small Arf GTPase-activating protein (SMAP) subfamily of Arf GTPase-activating proteins consists of closely related members, SMAP1 and SMAP2. These factors reportedly exert distinct functions in membrane trafficking, as manifested by different phenotypes seen in single knockout mice. The present study investigated whether SMAP proteins interact genetically. We report for the first time that simultaneous loss of SMAP1 and SMAP2 promotes apoptosis in the distal region of E7.5 mouse embryos, likely resulting in embryonic lethality. Thus, at least one SMAP gene, either SMAP1 or SMAP2, is required for proper embryogenesis.