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MARCKS phosphorylation by PKC strongly impairs cell polarity in the chick neural plate

Gonzalo Aparicio1,2, Cristina Arruti1, Flavio R Zolessi1,2

  • 1Laboratorio de Cultivo de Tejidos, Sección Biología Celular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.

Genesis (New York, N.Y. : 2000)
|April 1, 2018
PubMed

Insights

The protein MARCKS is crucial for neural tube closure during embryonic development. PKC activation disrupts its function, leading to developmental defects by affecting cell polarity and actin stability.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Neurulation, a critical embryonic process, relies on coordinated cellular movements.
  • The actin cytoskeleton is central to these movements, with MARCKS protein playing a known role.
  • MARCKS, a major PKC substrate, is essential for gastrulation and neurulation in various species.

Purpose of the Study:

  • To investigate the role of MARCKS protein in chick embryo neurulation.
  • To explore how Protein Kinase C (PKC) phosphorylation regulates MARCKS function during neural tube closure.
  • To elucidate the mechanisms by which MARCKS influences neuroepithelial cell polarity.

Main Methods:

  • Utilizing cultured chick embryos to study neurulation.
  • Employing Phorbol 12-myristate 13-acetate (PMA) to activate PKC.
  • Performing MARCKS knockdown and overexpressing nonphosphorylatable MARCKS mutants.
  • Analyzing neural plate cell polarity, apical cell extrusion, and F-actin organization.

Main Results:

  • PKC activation by PMA induced significant neural tube closure defects.
  • MARCKS phosphorylation and cytoplasmic redistribution occurred upon PKC activation.
  • Disrupted neuroepithelial polarity and increased apical cell extrusion were observed.
  • MARCKS knockdown mimicked the defects caused by PKC activation.
  • Overexpression of nonphosphorylatable MARCKS rescued PKC activation-induced cellular defects.

Conclusions:

  • MARCKS stabilizes subapical F-actin to maintain neuroepithelial polarity during neurulation.
  • PKC activation disrupts this stabilizing function, leading to neurulation defects.
  • MARCKS phosphorylation by PKC is a key regulatory mechanism impacting embryonic development.
Keywords:
actin filamentscell extrusionchick embryoneural tubeneuroepitheliumneurulation

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