Document Detail


Intracellular proadrenomedullin-derived peptides decorate the microtubules and contribute to cytoskeleton function.
MedLine Citation:
PMID:  18325988     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are secretory hormones, but it is not unusual to find them in intracellular compartments. Using yeast-2 hybrid technology, we found interactions between AM and several microtubule-associated proteins (MAPs), and between PAMP and tubulin. Expression of fluorescent-tagged AM and PAMP as well as immunofluorescence for the native peptides showed a complete decoration of the microtubules and colocalization with other MAPs. PAMP, but not AM, bound to tubulin in vitro and destabilized tubulin polymerization. Down-regulation of the gene coding for both AM and PAMP through small interfering RNA technology resulted in morphological changes, microtubule stabilization, increase in posttranslational modifications of tubulin such as acetylation and detyrosination, reduction in cell motility, and partial arrest at the G2 phase of the cell cycle, when compared with cells transfected with the same vector carrying a scrambled sequence. These results show that PAMP is a novel MAP, whereas AM may be exerting more subtle effects in regulating cytoskeleton function.
Authors:
Dan L Sackett; Laurent Ozbun; Enrique Zudaire; Lisa Wessner; John M Chirgwin; Frank Cuttitta; Alfredo Martínez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-06
Journal Detail:
Title:  Endocrinology     Volume:  149     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-21     Completed Date:  2008-08-08     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2888-98     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Integrative and Medical Biophysics, National Cancer Institute, Bethesda, Maryland 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma
Adrenomedullin / chemistry,  genetics,  physiology*
Animals
CHO Cells
COS Cells
Cell Line, Tumor
Cercopithecus aethiops
Cricetinae
Cricetulus
Cytoskeleton / physiology*
Haplorhini
Humans
Lung Neoplasms
Microtubules / physiology*
Peptide Fragments / physiology*
Protein Precursors / chemistry,  genetics,  physiology*
Chemical
Reg. No./Substance:
0/Peptide Fragments; 0/Protein Precursors; 0/proadrenomedullin; 148498-78-6/Adrenomedullin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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