PHOSPHORYLATION OF THE POLYMERIC IMMUNOGLOBULIN RECEPTOR REQUIRED FOR ITS EFFICIENT TRANSCYTOSIS

PHOSPHORYLATION OF THE POLYMERIC IMMUNOGLOBULIN RECEPTOR REQUIRED FOR ITS EFFICIENT TRANSCYTOSIS
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DOI:
10.1126/science.2110383
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发表时间:
1990-05-11
期刊:
影响因子:
56.9
通讯作者:
MOSTOV, KE
MOSTOV, KE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CASANOVA, JE;BREITFELD, PP;MOSTOV, KE

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极化上皮细胞的内体区室是膜运输的主要十字路口。从细胞表面进入该隔室的蛋白质被分选以运输到几个目的地之一:再循环到原始细胞表面,靶向溶酶体进行降解,或转胞吞到相反的表面。聚合免疫球蛋白受体(pIgR),这是正常的transcytosed从基底到顶端表面,被用作一个模型来剖析信号,介导这种分选事件。当外源性受体在Madin-Darby犬肾(MDCK)细胞中表达时,表明pIgR在位置664的丝氨酸残基处的磷酸化是有效转胞吞作用所需的。用丙氨酸取代丝氨酸产生一种受体,这种受体只能缓慢地转胞吞,并且似乎是再循环的。相反,用天冬氨酸(其模拟磷酸基团的负电荷)取代导致快速转胞吞作用。结论是磷酸化是指导pIgR从内体进入胞吞途径的信号。
The endosomal compartment of polarized epithelial cells is a major crossroads for membrane traffic. Proteins entering this compartment from the cell surface are sorted for transport to one of several destinations: recycling to the original cell surface, targeting to lysosomes for degradation, or transcytosis to the opposite surface. The polymeric immunoglobulin receptor (pIgR), which is normally transcytosed from the basolateral to the apical surface, was used as a model to dissect the signals that mediate this sorting event. When exogenous receptor was expressed in Madin-Darby Canine Kidney (MDCK) cells, it was shown that phosphorylation of pIgR at the serine residue at position 664 is required for efficient transcytosis. Replacement of this serine with alanine generated a receptor that is transcytosed only slowly, and appears to be recycled. Conversely, substitution with aspartic acid (which mimics the negative charge of the phosphate group) results in rapid transcytosis. It was concluded that phosphorylation is the signal that directs the pIgR from the endosome into the transcytotic pathway.