Knockdown of p180 Eliminates the Terminal Differentiation of a Secretory Cell Line

被引:38
作者
Benyamini, Payam [1 ]
Webster, Paul [2 ]
Meyer, David I. [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA
[2] House Ear Res Inst, Ahmanson Ctr Adv EM & Imaging, Los Angeles, CA 90057 USA
基金
美国国家卫生研究院;
关键词
UNFOLDED-PROTEIN-RESPONSE; ROUGH ENDOPLASMIC-RETICULUM; DEVELOPING RAT HEPATOCYTE; PANCREATIC EXOCRINE CELL; HUMAN LEUKEMIA-CELLS; SACCHAROMYCES-CEREVISIAE; RIBOSOME RECEPTOR; PHOSPHOLIPID BIOSYNTHESIS; FUNCTIONAL-CHARACTERIZATION; APOLIPOPROTEIN-E;
D O I
10.1091/mbc.E08-07-0682
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have previously reported that the expression in yeast of an integral membrane protein (p180) of the endoplasmic reticulum (ER), isolated for its ability to mediate ribosome binding, is capable of inducing new membrane biogenesis and an increase in secretory capacity. To demonstrate that p180 is necessary and sufficient for terminal differentiation and acquisition of a secretory phenotype in mammalian cells, we studied the differentiation of a secretory cell line where p180 levels had been significantly reduced using RNAi technology and by transiently expressing p180 in nonsecretory cells. A human monocytic (THP-1) cell line, that can acquire macrophage-like properties, failed to proliferate rough ER when p180 levels were lowered. The Golgi compartment and the secretion of apolipoprotein E (Apo E) were dramatically affected in cells expressing reduced p180 levels. On the other hand, expression of p180 in a human embryonic kidney nonsecretory cell line (HEK293) showed a significant increase in proliferation of rough ER membranes and Golgi complexes. The results obtained from knockdown and overexpression experiments demonstrate that p180 is both necessary and sufficient to induce a secretory phenotype in mammalian cells. These findings support a central role for p180 in the terminal differentiation of secretory cells and tissues.
引用
收藏
页码:732 / 744
页数:13
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