Fat2 acts through the WAVE regulatory complex to drive collective cell migration during tissue rotation

Squarr, Anna Julia; Brinkmann, Klaus; Chen, Baoyu; Steinbacher, Tim; Ebnet, Klaus; Rosen, Michael K.; Bogdan, Sven

doi:10.1083/jcb.201508081

Cited by 58 publications

(97 citation statements)

References 34 publications

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“…We have not excluded an additional role in actin regulation other than polarized alignment; the requirement for Fat2 and actin but not MTs to maintain rotation, as well as the direct binding of actin regulators by vertebrate Fat1, a possible ortholog of Drosophila Fat2 (Moeller et al, 2004; Tanoue and Takeichi, 2004), suggests such a role. Moreover, while this work was in revision, Squarr et al (2016) showed that Fat2 can directly influence the actin cytoskeleton via binding to the WAVE complex.…”

Section: Discussionmentioning

confidence: 88%

Symmetry Breaking in an Edgeless Epithelium by Fat2-Regulated Microtubule Polarity

et al. 2016

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Planar cell polarity (PCP) information is a critical determinant of organ morphogenesis. While PCP in bounded epithelial sheets is increasingly well-understood, how PCP is organized in tubular and acinar tissues is not. Drosophila egg chambers (follicles) are an acinus-like ‘edgeless epithelium’ and exhibit a continuous, circumferential PCP that does not depend on pathways active in bounded epithelia; this follicle PCP directs formation of an ellipsoid rather than a spherical egg. Here we apply a novel imaging algorithm to ‘unroll’ the entire 3D tissue surface and comprehensively analyze PCP onset. This approach traces chiral symmetry-breaking to plus-end polarity of microtubules in the germarium, well before follicles form and rotate. PCP germarial microtubules provide chiral information that predicts the direction of whole-tissue rotation as soon as independent follicles form. Concordant microtubule polarity, but not microtubule alignment, requires the atypical cadherin Fat2, which acts at an early stage to translate plus-end bias into coordinated actin-mediated collective cell migration. Because microtubules are not required for PCP or migration after follicle rotation initiates, while dynamic actin and extracellular matrix are, polarized microtubules lie at the beginning of a handoff mechanism that passes early chiral PCP of the cytoskeleton to a supracellular planar polarized extracellular matrix and elongates the organ.

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Section: Discussionmentioning

confidence: 88%

Symmetry Breaking in an Edgeless Epithelium by Fat2-Regulated Microtubule Polarity

et al. 2016

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“…In addition, a WRC-interacting receptor sequence (WIRS) was identified in a number of membrane receptors that directly bind to the WRC components CYFIP1 and ABI1/ABI2 (Chen et al, 2014). Significantly, FAT2 (also known as Kugelei) contains such an element, and through this interaction, the WRC drives collective cell migration in Drosophila (Squarr et al, 2016).…”

Section: Jmymentioning

confidence: 99%

Cellular functions of WASP family proteins at a glance

Alekhina

Burstein

Billadeau

2017

Journal of Cell Science

181

172

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Proteins of the Wiskott–Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network. Recent studies have also identified roles for WASP family members in promoting actin dynamics at the centrosome, influencing nuclear shape and membrane remodeling events leading to the generation of autophagosomes. Interestingly, several WASP family members have also been observed in the nucleus where they directly influence gene expression by serving as molecular platforms for the assembly of epigenetic and transcriptional machinery. In this Cell Science at a Glance article and accompanying poster, we provide an update on the subcellular roles of WHAMM, JMY and WASH (also known as WASHC1), as well as their mechanisms of regulation and emerging functions within the cell.

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“…A recent paper proposed that dFat2 promotes follicle cell migration similarly to the way that the mammalian proteins function [28]. Although dFat2 lacks Ena/VASP binding sites in its ICD [15], it does have predicted binding sites for the Wave regulatory complex (WRC) [28,29], which helps to build the branched actin network found in lamellipodial protrusions.…”

Section: Introductionmentioning

confidence: 99%

“…Although dFat2 lacks Ena/VASP binding sites in its ICD [15], it does have predicted binding sites for the Wave regulatory complex (WRC) [28,29], which helps to build the branched actin network found in lamellipodial protrusions. Consistent with this observation, this paper showed that dFat2 is required for the formation of protrusions at the leading edge of each follicle cell, and that the WRC binds to dFat2’s ICD in vitro [28]. From these data and others, the authors concluded that dFat2 stimulates the formation of leading edge protrusions on a cell-autonomous basis by recruiting an actin assembly factor to its ICD.…”

Section: Introductionmentioning

confidence: 99%

“…Although dFat2’s role in the nervous system has not yet been explored, it is widely expressed in Drosophila neurons [43]. Given that dFat2’s ICD binds to the WRC [28], and that Fat1’s and Fat3’s ICDs also have predicted WRC binding sites [29], all three proteins might influence neuronal development via cell-autonomous polarization of the F-actin assembly, as proposed for Fat3 in amacrine cells [23]. Moreover, since Lar plays critical roles in axon guidance and synapse formation [44–46], it is interesting to speculate that Fat-like cadherins could interact with Lar to guide neuronal connectivity as well.…”

Section: Introductionmentioning

confidence: 99%

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Fat-like cadherins in cell migration—leading from both the front and the back

Horne‐Badovinac

2017

Current Opinion in Cell Biology

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When cells migrate through the body, their motility is continually influenced by interactions with other cells. The Fat-like cadherins are cell-cell signaling proteins that promote migration in multiple cell types. Recent studies suggest, however, that Fat-like cadherins influence motility differently in mammals versus Drosophila with the cadherin acting at the leading edge of mammalian cells and the trailing edge of Drosophila cells. As opposed to this being a difference between organisms, it is more likely that the Fat-like cadherins are highly versatile proteins that can interact with the migration machinery in multiple ways. Here, I review what is known about how Fat-like cadherins promote migration, and then explore where conserved features may be found between the mammalian and Drosophila models.

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Fat2 acts through the WAVE regulatory complex to drive collective cell migration during tissue rotation

Abstract: The atypical cadherin Fat2 binds the WAVE regulatory complex (WRC) and acts with receptor tyrosine phosphatase Dlar through the WRC to control collective cell migration during Drosophila oogenesis.

Cited by 58 publications

References 34 publications

Symmetry Breaking in an Edgeless Epithelium by Fat2-Regulated Microtubule Polarity

Symmetry Breaking in an Edgeless Epithelium by Fat2-Regulated Microtubule Polarity

Cellular functions of WASP family proteins at a glance

Fat-like cadherins in cell migration—leading from both the front and the back

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