Developmentally regulated GTP-binding protein 1 modulates ciliogenesis via an interaction with Dishevelled

Abstract

Cilia are critical for proper embryonic development and maintaining homeostasis. Although extensively studied, there are still significant gaps regarding the proteins involved in regulating ciliogenesis. Using the Xenopus laevis embryo, we show that Dishevelled (Dvl), a key Wnt signaling scaffold that is critical to proper ciliogenesis, interacts with Drg1 (developmentally regulated GTP-binding protein 1). The loss of Drg1 or disruption of the interaction with Dvl reduces the length and number of cilia and displays defects in basal body migration and docking to the apical surface of multiciliated cells (MCCs). Moreover, Drg1 morphants display abnormal rotational polarity of basal bodies and a decrease in apical actin and RhoA activity that can be attributed to disruption of the protein complex between Dvl and Daam1, as well as between Daam1 and RhoA. These results support the concept that the Drg1–Dvl interaction regulates apical actin polymerization and stability in MCCs. Thus, Drg1 is a newly identified partner of Dvl in regulating ciliogenesis.

Divergent roles of the Wnt/PCP Formin Daam1 in renal ciliogenesis

“…Prior work demonstrated that within multicilliated cells of the Xenopus skin Daam1, a component of the planar cell polarity pathway, is important for the proper development of motile cilia [26,39]. Additionally, the cilia have been found to be important for cell polarity and cell divisions [9,40].…”

m6A-dependent up-regulation of DRG1 by METTL3 and ELAVL1 promotes growth, migration, and colony formation in osteosarcoma

“…It is a highly conserved gene that is expressed in almost all tissues. DRG1 plays an important role during embryonic development [3][4][5]. Although DRG1 is down-regulated after birth, high expression of DRG1 is observed in rapidly growing tissues and organs [6].…”

Developmentally regulated GTPases: structure, function and roles in disease

“…Interestingly, DRG1 has also been implicated in the regulation of cilia [ 80 ]. Cilia are long, thin, microtubule structures that protrude from the surface of cells where they are important for signalling pathways and development [ 81 ].…”

“…Cilia are long, thin, microtubule structures that protrude from the surface of cells where they are important for signalling pathways and development [ 81 ]. Lee et al suggested that DRG1 promotes the formation of cilia independently of its GTPase activity, through an interaction with the Wnt signalling activator Dishevelled (Dvl) [ 80 ]. DRG1 and Dvl interact with the protein Daam1 (Dishevelled-associated activator of morphogenesis 1), which in turn promotes the formation of the apical actin network that is required for proper basal body localization and cilia formation [ 80 ].…”