Spatial regulation of the polarity kinase PAR-1 by parallel inhibitory mechanisms

Andrew W. Folkmann, Geraldine Seydoux

Research output: Contribution to journalArticle

Abstract

The MARK/PAR-1 family of kinases are conserved regulators of cell polarity that share a conserved C-terminal kinase-associated domain (KA1). Localization of MARK/PAR-1 kinases to specific regions of the cell cortex is a hallmark of polarized cells. In Caenorhabditiselegans zygotes, PAR-1 localizes to the posterior cortex under the influence of another polarity kinase, aPKC/PKC-3. Here, we report that asymmetric localization of PAR-1 protein is not essential, and that PAR-1 kinase activity is regulated spatially. We find that, as in human MARK1, the PAR-1 KA1 domain is an auto-inhibitory domain that suppresses kinase activity. Auto-inhibition by the KA1 domain functions in parallel with phosphorylation by PKC-3 to suppress PAR-1 activity in the anterior cytoplasm. The KA1 domain also plays an additional role that is essential for germ plasm maintenance and fertility. Our findings suggest that modular regulation of kinase activity by redundant inhibitory inputs contributes to robust symmetry breaking by MARK/PAR-1 kinases in diverse cell types.

Original languageEnglish (US)
JournalDevelopment (Cambridge, England)
Volume146
Issue number6
DOIs
StatePublished - Mar 25 2019

Fingerprint

Phosphotransferases
Cell Polarity
Zygote
Fertility
Cytoplasm
Maintenance
Phosphorylation
Proteins

Keywords

  • Kinase
  • MEX-6
  • P granules
  • PAR proteins
  • PAR-3
  • Polarity

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Spatial regulation of the polarity kinase PAR-1 by parallel inhibitory mechanisms. / Folkmann, Andrew W.; Seydoux, Geraldine.

In: Development (Cambridge, England), Vol. 146, No. 6, 25.03.2019.

Research output: Contribution to journalArticle

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