Nonredundant roles of DIAPHs in primary ciliogenesis

J Biol Chem. 2021 Jan-Jun:296:100680. doi: 10.1016/j.jbc.2021.100680. Epub 2021 Apr 17.

Abstract

Primary cilia are hubs for several signaling pathways, and disruption in cilia function and formation leads to a range of diseases collectively known as ciliopathies. Both ciliogenesis and cilia maintenance depend on vesicle trafficking along a network of microtubules and actin filaments toward the basal body. The DIAPH (Diaphanous-related) family of formins promote both actin polymerization and microtubule (MT) stability. Recently, we showed that the formin DIAPH1 is involved in ciliogenesis. However, the role of other DIAPH family members in ciliogenesis had not been investigated. Here we show that depletion of either DIAPH2 or DIAPH3 also disrupted ciliogenesis and cilia length. DIAPH3 depletion also reduced trafficking within cilia. To specifically examine the role of DIAPH3 at the base, we used fused full-length DIAPH3 to centrin, which targeted DIAPH3 to the basal body, causing increased trafficking to the ciliary base, an increase in cilia length, and formation of bulbs at the tips of cilia. Additionally, we confirmed that the microtubule-stabilizing properties of DIAPH3 are important for its cilia length functions and trafficking. These results indicate the importance of DIAPH proteins in regulating cilia maintenance. Moreover, defects in ciliogenesis caused by DIAPH depletion could only be rescued by expression of the specific family member depleted, indicating nonredundant roles for these proteins.

Keywords: DIAPH2; DIAPH3; cilia; cilia maintenance; ciliogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cell Line
  • Cilia / metabolism*
  • Formins / metabolism*
  • Humans
  • Microtubules / metabolism

Substances

  • Actins
  • Formins