RECS1 deficiency in mice induces susceptibility to cystic medial degeneration.
RECS1 deficiency in mice induces susceptibility to cystic medial degeneration.
复制标题
DOI：
10.1266/ggs.81.41
复制
发表时间：
2006-02
影响因子：
1.1
通讯作者：
Hanjun Zhao;A. Ito;S. H. Kimura;N. Yabuta;N. Sakai;M. Ikawa;M. Okabe;Y. Matsuzawa;S. Yamashita;H. Nojima
中科院分区：
文献类型：
--
作者：
Hanjun Zhao;A. Ito;S. H. Kimura;N. Yabuta;N. Sakai;M. Ikawa;M. Okabe;Y. Matsuzawa;S. Yamashita;H. Nojima
RECS1是一个新的剪应力反应基因，编码一种蛋白质，可能形成七跨跨膜结构域。我们在此报道了小鼠RECS1(MRECS1)转录本在除胸腺、脾和睾丸以外的大多数组织中都被检测到。推测mRECS1的N末端含有较高的氨基酸残基(23%)和12%的甘氨酸(12%)，含有一个PPXY基序和多个PXXP基序，以及一个重叠的P(T/S)AP和P(T/S)APPXY基序。PPXY基序位于一个潜在的害虫序列中(害虫得分：+7.65)。我们制备了抗RECS1的多克隆抗体，经免疫印迹分析发现，肺和主动脉中的mRECS1蛋白均为34.4 kDa条带。而在心脏和肝脏中分别检测到一条移位的58 kDa或三条移位的带(48、69、82 kDa)。由于Northern印迹只在心脏和肝脏组织以及其他组织(约2.2kb)中检测到一种mRECS1 mRNA，因此分子量的差异似乎是翻译后修饰的结果。生化分离和RECS1-GFP融合蛋白分析表明，RECS1定位于细胞质的内切/溶酶体膜。为了了解RECS1在体内的功能，我们制作了RECS1基因敲除(KO)小鼠，发现RECS1基因敲除(KO)小鼠(大于14月龄)容易发生囊性内侧变性(CMD)。综上所述，我们认为RECS1是一种内体/溶酶体膜蛋白，在血管重塑中起保护作用。
RECS1 is a novel shear stress-responsive gene that encodes a protein putatively forming seven-span transmembrane domains. We reports here that mouse RECS1 (mRECS1) transcripts is detected in most tissues except for thymus, spleen and testis. The putative cytoplasmic N-terminus of mRECS1 has a high content of proline (23%) and glycine (12%) residues, contains one PPXY motif, multiple PXXP motifs and one overlapping P(T/S)AP and PPXY motif (P(T/S)APPXY). The PPXY motif lies within one potential PEST sequence (PEST score: +7.65). We prepared anti-RECS1 polyclonal antibody and found by western blot analysis that the mRECS1 protein in the lung and aorta was detected as a 34.4 kDa band. However, one shifted 58 kDa band or three shifted bands (48, 69, 82 kDa) were detected in the heart or the liver, respectively. Since northern blot detected only one species of mRECS1 mRNA in heart and liver tissues, as well as other tissues (approximately 2.2 kb), these differences in molecular weight seem to be due to posttranslational modification. Biochemical fractionation and RECS1-GFP fusion protein revealed that RECS1 localizes at the endosomal/lysosomal membranes in the cytoplasm. To understand the function of RECS1 in the body, we made RECS1 knockout (KO) mice and found that RECS1 KO mice (older than 14 months) are prone to cystic medial degeneration (CMD). Taken together, we conclude that RECS1 is an endosomal/lysosomal membrane protein which plays protective roles in vascular remodeling.