The small molecule AMBMP disrupts microtubule growth, ciliogenesis, cell polarity, and cell migration

Cytoskeleton (Hoboken). 2018 Oct;75(10):450-457. doi: 10.1002/cm.21496.

Abstract

2-Amino-4-(3,4-[methylenedioxy]benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP) is a small molecule that has been previously reported to be both a Wnt agonist and a microtubule (MT) regulator. Here we report a detailed analysis of AMBMPs effects on MTs and on MT associated cellular processes including cell polarity, ciliogenesis, and cell migration. Specifically, treatment of Xenopus embryos with AMBMP leads to defects similar to the MT depolymerizing drug nocodazole, including a failure to generate or polarize cilia (depending on the timing of treatment) and a loss of the cell movements associated with radial intercalation. The dramatic effect AMBMP has on basic MT based cellular functions suggests that its usefulness as a Wnt regulator is questionable. Moreover, it may be an important new tool for experimental or pharmacological manipulation of MTs.

Keywords: Wnt signaling; cell polarity; ciliogenesis; microtubule; small molecule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodioxoles / pharmacology*
  • Cell Movement / drug effects*
  • Cell Polarity / drug effects
  • Cilia / drug effects*
  • Cilia / metabolism
  • Humans
  • Microtubules / drug effects*
  • Microtubules / metabolism
  • Pyrimidines / pharmacology*
  • Wnt Signaling Pathway / drug effects
  • Xenopus

Substances

  • 2-amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine
  • Benzodioxoles
  • Pyrimidines