Intracellular proadrenomedullin-derived peptides decorate the microtubules and contribute to cytoskeleton function

Dan L. Sackett, Laurent Ozbun, Enrique Zudaire, Lisa Wessner, John Chirgwin, Frank Cuttitta, Alfredo Martínez

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 maybe exerting more subtle effects in regulating cytoskeleton function.

Original languageEnglish (US)
Pages (from-to)2888-2898
Number of pages11
JournalEndocrinology
Volume149
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Fingerprint

Adrenomedullin
Cytoskeleton
Microtubules
Peptides
Tubulin
Microtubule-Associated Proteins
Technology
G2 Phase
Post Translational Protein Processing
Acetylation
proadrenomedullin
Polymerization
Small Interfering RNA
Cell Movement
Fluorescent Antibody Technique
Pathogen-Associated Molecular Pattern Molecules
Cell Cycle
Down-Regulation
Yeasts
Hormones

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Intracellular proadrenomedullin-derived peptides decorate the microtubules and contribute to cytoskeleton function. / Sackett, Dan L.; Ozbun, Laurent; Zudaire, Enrique; Wessner, Lisa; Chirgwin, John; Cuttitta, Frank; Martínez, Alfredo.

In: Endocrinology, Vol. 149, No. 6, 06.2008, p. 2888-2898.

Research output: Contribution to journalArticle

Sackett, DL, Ozbun, L, Zudaire, E, Wessner, L, Chirgwin, J, Cuttitta, F & Martínez, A 2008, 'Intracellular proadrenomedullin-derived peptides decorate the microtubules and contribute to cytoskeleton function', Endocrinology, vol. 149, no. 6, pp. 2888-2898. https://doi.org/10.1210/en.2007-1763
Sackett, Dan L. ; Ozbun, Laurent ; Zudaire, Enrique ; Wessner, Lisa ; Chirgwin, John ; Cuttitta, Frank ; Martínez, Alfredo. / Intracellular proadrenomedullin-derived peptides decorate the microtubules and contribute to cytoskeleton function. In: Endocrinology. 2008 ; Vol. 149, No. 6. pp. 2888-2898.
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AU - Martínez, Alfredo

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