ERK7 regulates ciliogenesis by phosphorylating the actin regulator CapZIP in cooperation with Dishevelled

Nat Commun. 2015 Mar 31:6:6666. doi: 10.1038/ncomms7666.

Abstract

Cilia are essential for embryogenesis and maintenance of homeostasis, but little is known about the signalling pathways that regulate ciliogenesis. Here, we identify ERK7, an atypical mitogen-activated protein kinase, as a key regulator of ciliogenesis. ERK7 is strongly expressed in ciliated tissues of Xenopus embryos. ERK7 knockdown markedly diminishes both the number and the length of cilia in multiciliated cells, and it inhibits the apical migration of basal bodies. Moreover, ERK7 knockdown results in a loss of the apical actin meshwork, which is required for the proper migration of basal bodies. We find that the actin regulator CapZIP, which has been shown to regulate ciliogenesis in a phosphorylation-dependent manner, is an ERK7 substrate, and that Dishevelled, which has also been shown to regulate ciliogenesis, facilitates ERK7 phosphorylation of CapZIP through binding to both ERK7 and CapZIP. Collectively, these results identify an ERK7/Dishevelled/CapZIP axis that regulates ciliogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Basal Bodies / metabolism
  • Base Sequence
  • Cilia / genetics*
  • Cilia / metabolism
  • Dishevelled Proteins
  • Embryo, Nonmammalian
  • Extracellular Signal-Regulated MAP Kinases / genetics*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Knockdown Techniques
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Molecular Sequence Data
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • RNA, Messenger / metabolism*
  • Xenopus Proteins / genetics*
  • Xenopus Proteins / metabolism
  • Xenopus laevis

Substances

  • Adaptor Proteins, Signal Transducing
  • Dishevelled Proteins
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • RCSD1 protein, Xenopus
  • RNA, Messenger
  • Xenopus Proteins
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 3

Associated data

  • GENBANK/AB920341