Hepatocystin is Essential for TRPM7 Function During Early Embryogenesis.
Hepatocystin is Essential for TRPM7 Function During Early Embryogenesis.
复制标题
肝囊素对于早期胚胎发生期间 TRPM7 的功能至关重要。
DOI：
10.1038/srep18395
复制
发表时间：
2015
影响因子：
4.6
通讯作者：
Runnels,LorenW
中科院分区：
文献类型：
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作者：
Overton,JeffreyD;Komiya,Yuko;Mezzacappa,Courtney;Nama,Kaushik;Cai,Na;Lou,Liping;Fedeles,SorinV;Habas,Raymond;Runnels,LorenW
蛋白激酶C底物80K-H （PRKCSH）编码一种名为肝囊素（80K-H，PRKCSH）的80 KDa蛋白，其突变可引起多囊性肝病（PCLD）。肝囊素是葡萄糖苷酶II的非催化β亚基，葡萄糖苷酶II是一种内质网驻留酶，参与新合成糖蛋白的加工和质量控制。携带prkcshare杂合子种系突变的患者被认为由于第二个等位基因的体细胞缺失而产生肾囊肿，这随后会干扰TRP通道多囊蛋白-2 （PKD2）的表达。prkcshin小鼠的两个等位基因的缺失导致胚胎日E11.5之前的胚胎死亡。在这里，我们研究了肝囊素在非洲爪蟾胚胎发生过程中的功能，并确定肝囊素是TRPM7离子通道的结合伙伴，其功能是脊椎动物原肠胚形成所必需的。我们发现TRPM7与肝囊素协同作用。尽管其他n -糖基化蛋白对早期发育至关重要，但TRPM7在非洲爪蟾胚胎中的过表达足以完全挽救因肝囊素缺失而导致的原肠胚发育缺陷。我们观察到，在xenopuslaevis胚胎中，肝胱抑素的缺失降低了TRPM7的表达，这表明肝胱抑素缺失导致的早期胚胎致死主要是由于TRPM7蛋白表达受损。
Mutations inprotein kinase C substrate 80K-H (PRKCSH), which encodes for an 80 KDa protein named hepatocystin (80K-H,PRKCSH), gives rise to polycystic liver disease (PCLD). Hepatocystin functions as the noncatalytic beta subunit of Glucosidase II, an endoplasmic reticulum (ER)-resident enzyme involved in processing and quality control of newly synthesized glycoproteins. Patients harboring heterozygous germline mutations inPRKCSHare thought to develop renal cysts as a result of somatic loss of the second allele, which subsequently interferes with expression of the TRP channel polycystin-2 (PKD2). Deletion of both alleles ofPRKCSHin mice results in embryonic lethality before embryonic day E11.5. Here, we investigated the function of hepatocystin duringXenopus laevisembryogenesis and identified hepatocystin as a binding partner of the TRPM7 ion channel, whose function is required for vertebrate gastrulation. We find that TRPM7 functions synergistically with hepatocystin. Although other N-glycosylated proteins are critical to early development, overexpression of TRPM7 inXenopus laevisembryos was sufficient to fully rescue the gastrulation defect caused by loss of hepatocystin. We observed that depletion of hepatocystin inXenopuslaevis embryos decreased TRPM7 expression, indicating that the early embryonic lethality caused by loss of hepatocystin is mainly due to impairment of TRPM7 protein expression.
DOI：
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发表时间：
1966
期刊：
影响因子：
--
作者：
G. Cantoni;D. R. Davies
通讯作者：
D. R. Davies