CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels

Elife. 2021 Jul 14:10:e63731. doi: 10.7554/eLife.63731.


CEP78 is a centrosomal protein implicated in ciliogenesis and ciliary length control, and mutations in the CEP78 gene cause retinal cone-rod dystrophy associated with hearing loss. However, the mechanism by which CEP78 affects cilia formation is unknown. Based on a recently discovered disease-causing CEP78 p.L150S mutation, we identified the disease-relevant interactome of CEP78. We confirmed that CEP78 interacts with the EDD1-DYRK2-DDB1VPRBP E3 ubiquitin ligase complex, which is involved in CP110 ubiquitination and degradation, and identified a novel interaction between CEP78 and CEP350 that is weakened by the CEP78L150S mutation. We show that CEP350 promotes centrosomal recruitment and stability of CEP78, which in turn leads to centrosomal recruitment of EDD1. Consistently, cells lacking CEP78 display significantly increased cellular and centrosomal levels of CP110, and depletion of CP110 in CEP78-deficient cells restored ciliation frequency to normal. We propose that CEP78 functions downstream of CEP350 to promote ciliogenesis by negatively regulating CP110 levels via an EDD1-dependent mechanism.

Keywords: CEP350; CEP78; CP110; cell biology; centrosome; cilia; human; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cilia / metabolism*
  • Gene Knockout Techniques
  • Humans
  • Microtubule Proteins / genetics
  • Microtubule Proteins / metabolism*
  • Microtubule-Associated Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / metabolism*
  • Ubiquitination


  • CCP110 protein, human
  • CEP350 protein, human
  • CEP78 protein, human
  • Cell Cycle Proteins
  • Microtubule Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Phosphoproteins

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.