QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 20, Issue 2, 732-744, January 15, 2009

This Article Full Text Full Text (PDF) All Versions of this Article: E08-07-0682v1 20/2/732    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Benyamini, P. Articles by Meyer, D. I. Search for Related Content PubMed PubMed Citation Articles by Benyamini, P. Articles by Meyer, D. I.

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

Payam Benyamini^*, Paul Webster, and David I. Meyer^*

*Department of Biological Chemistry, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; and Ahmanson Center for Advanced EM and Imaging, House Ear Institute, Los Angeles, CA 90057

Submitted July 3, 2008; Revised October 29, 2008; Accepted November 13, 2008
Monitoring Editor: Jean E. Gruenberg

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.

Address correspondence to: David I. Meyer (dimeyer{at}ucla.edu)

Abbreviations used: ER, endoplasmic reticulum; TPA, 12-O-tetradecanoylphorbol-13-acetate; THP-1, cell line derived from human acute monocytic leukemia; shRNA, small-hairpin RNA.