The ArfGAP Drongo Promotes Actomyosin Contractility during Collective Cell Migration by Releasing Myosin Phosphatase from the Trailing Edge

Abstract

Highlights d The ArfGAP Drongo is required for the normal migration of border cell clusters d Drongo specifically affects the contractility at the back of the cluster d Loss of Drongo increases myosin phosphatase at the back of the BC cluster d Drongo acts antagonistically to the GEF Steppke on Arf51F to promote contractility

The Arf-GEF Steppke promotes F-actin accumulation, cell protrusions and tissue sealing during Drosophila dorsal closure

“…Significantly, in vivo mouse studies have shown that expression of constitutively active Arf6 can promote invasion of cancer cells into healthy tissue [24]. Not only does Arf small G protein signaling promote protrusive cellular activity, but it also antagonizes cellular contractility [25][26][27][28][29][30]. These effects are relevant to the transitioning of tissues between jammed, fluid and dissociated states [60], and plasma membrane Arf small G protein signaling seems to play a central role in tuning epithelial dynamics during development and disease.…”

“…In Drosophila, this down-regulation controls early embryo pseudo-cleavage [25], budding of primordial germline cells [26], epidermal spreading at dorsal closure (DC) and head involution [27], and junctional actomyosin networks in the wing disc [28]. Reciprocally, an Arf GTPase activating protein, Drongo, promotes actomyosin networks at the rear of border cell clusters [29]. During zebrafish embryo epiboly, cytohesins down-regulate junctional actomyosin and promote tissue spreading [27], and in cultured mammalian cells, cytohesin activity downregulates actomyosin activity to allow podosome protrusion [30].…”

ArfGAP1 regulates the endosomal sorting of guidance receptors to promote directed collective cell migration in vivo

“…In previous work, we and others have shown that vesicular trafficking plays an important role in regulating border cell migration (Assaker et al, 2010; Cobreros-Reguera et al, 2010; Janssens et al, 2010; Jekely et al, 2005; Laflamme et al, 2012; Ramel et al, 2013; Wan et al, 2013; Zeledon et al, 2019). In particular, endocytosis and recycling were shown to regulate the level and the distribution of active RTKs at the plasma membrane and hence to be required for directed migration (Assaker et al, 2010; Janssens et al, 2010; Jekely et al, 2005; Laflamme et al, 2012; Wan et al, 2013).…”

“…Despites several candidates inducing pleiotropic effects, as expected since Arf GTPases are required to form vesicles in the biosynthetic pathway (Jackson and Bouvet, 2014; Rodrigues and Harris, 2019), we found that a few candidates induced specific phenotypes. For example, we found that the GAP Drongo was required to promote contractility at the onset of border cell migration (Zeledon et al, 2019). In the present study, we focus on ArfGAP1.…”

Collective border cell migration requires the zinc transporter Catsup to limit endoplasmic reticulum stress

“…Genetic screens have yielded insights into the molecular mechanisms that specify which of the ~850 follicle cells acquire the ability to migrate 5,6 , the developmental timing of the migration 7,8 , collective direction sensing, and cytoskeletal dynamics [9][10][11][12][13][14][15][16][17][18][19] . While much is understood, insights continue to emerge from border cell studies [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] . The gene catsup was identified both in a large-scale, ethyl methanesulfonate-induced mutagenesis screen for border cell migration defects in mosaic clones 35 and in a whole-genome gene expression profile 36 .…”