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

Development. 2019 Mar 25;146(6):dev171116. doi: 10.1242/dev.171116.

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 Caenorhabditis elegans 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.

Keywords: Kinase; MEX-6; P granules; PAR proteins; PAR-3; Polarity.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Lineage
  • Cell Polarity*
  • Cytoplasm / metabolism
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins
  • Humans
  • Microscopy, Confocal
  • Mutation
  • Phosphorylation
  • Protein Domains
  • Protein Kinase C / physiology
  • Protein Serine-Threonine Kinases / physiology*
  • RNA Interference
  • Threonine / chemistry

Substances

  • Caenorhabditis elegans Proteins
  • Green Fluorescent Proteins
  • Threonine
  • MARK1 protein, human
  • PAR-1 protein, C elegans
  • Protein Serine-Threonine Kinases
  • PKC-3 protein
  • Protein Kinase C