help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on February 28, 2008, doi:10.1165/rcmb.2007-0139OC

Am. J. Respir. Cell Mol. Biol., Volume 39, Number 1, July 2008, 68-76

A more recent version of this article appeared on July 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2007-0139OCv1
39/1/68    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Park, J.
Right arrow Articles by Adler, K. B
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Park, J.
Right arrow Articles by Adler, K. B

Submitted on April 20, 2007
Revised on February 21, 2008

Marcks Regulation of Mucin Secretion by Airway Epithelium in vitro: Interaction with Chaperones

Joungjoa Park1, Shijing Fang1, Anne L Crews1, Ko-Wei Lin1, and Kenneth B Adler1*

1 Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, United States

* To whom correspondence should be addressed. E-mail: kenneth_adler{at}ncsu.edu.

We have reported previously that MARCKS (Myristoylated Alanine-Rich C Kinase Substrate) is a key regulatory molecule controlling mucin secretion by airway epithelial cells in vitro and in vivo. The results of those studies supported a mechanism whereby MARCKS, upon phosphorylation by protein kinase C (PKC), translocates from plasma membrane to cytoplasm, where its binding to membranes of intracellular mucin granules is a key component of the secretory pathway. It remains unknown how MARCKS is targeted to and/or preferentially attaches to mucin granule membranes. We hypothesized the chaperone Cysteine String Protein (CSP) may play an important role in this process. CSP was shown to associate with membranes of intracellular mucin granules in well-differentiated normal human bronchial epithelial (NHBE) cells in vitro, as determined by ultrastructural immunohistochemistry and Western blotting of isolated granule membranes. CSP in these cells complexed with MARCKS, as shown by co-immunoprecipitation. Given reported associations between CSP and a second chaperone, Heat Shock Protein 70 (HSP70), a role for HSP70 in the MARCKS-dependent secretory mechanism also was investigated. HSP70 appeared to form a trimeric complex with MARCKS and CSP associated with mucin granule membranes within airway epithelial cells. Transfection of the HBE1 human bronchial epithelial cell line with siRNAs targeting sequences of MARCKS, CSP, or HSP70 resulted, in each case, in significant knockdown of expression of these proteins and subsequent attenuation of mucin secretion. The results provide the first evidence that CSP and HSP70, and their interactions with MARCKS, are involved in mucin secretion.




This article has been cited by other articles:


Home page
 DevelopmentHome page
J. M. Weimer, Y. Yokota, A. Stanco, D. J. Stumpo, P. J. Blackshear, and E.S. Anton
MARCKS modulates radial progenitor placement, proliferation and organization in the developing cerebral cortex
Development, September 1, 2009; 136(17): 2965 - 2975.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Ahmad, A. Ahmad, E. S. Dremina, V. S. Sharov, X. Guo, T. N. Jones, J. E. Loader, J. R. Tatreau, A.-L. Perraud, C. Schoneich, et al.
Bcl-2 Suppresses Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase Expression in Cystic Fibrosis Airways: Role in Oxidant-mediated Cell Death
Am. J. Respir. Crit. Care Med., May 1, 2009; 179(9): 816 - 826.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
E. Meimaridou, S. B Gooljar, and J P. Chapple
From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery
J. Mol. Endocrinol., January 1, 2009; 42(1): 1 - 9.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Kesimer, S. Kirkham, R. J. Pickles, A. G. Henderson, N. E. Alexis, G. DeMaria, D. Knight, D. J. Thornton, and J. K. Sheehan
Tracheobronchial air-liquid interface cell culture: a model for innate mucosal defense of the upper airways?
Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L92 - L100.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2008 American Thoracic Society. 		  SOTA, FL