Specifying one oocyte from many In many animals, only one cell from a cyst of germ cells is selected to become the oocyte. Using fruit flies as a model, Nashchekin et al . identified the microtubule minus end-binding protein Patronin/CAMSAP as a key factor for specifying oocyte fate. Patronin amplifies an initial asymmetry provided by the fusome to form a noncentrosomal microtubule network focused on one cell, along which dynein transports oocyte fate determinants. This mechanism for selecting a single oocyte may be shared in other organisms. —BAP

Cell polarity is the asymmetric distribution of cellular components along a defined axis. Polarity relies on complex signalling networks between conserved patterning proteins, including the PAR ( par titioning defective) proteins, which become segregated in response to upstream symmetry breaking cues. Although the mechanisms that drive the asymmetric localization of these proteins are dependent upon cell type and context, in many cases the regulation of actomyosin cytoskeleton dynamics is central to the transport, recruitment and/or stabilization of these polarity effectors into defined subcellular domains. The transport or advection of PAR proteins by an actomyosin flow was first observed in the Caenorhabditis elegan s zygote more than a decade ago. Since then a multifaceted approach, using molecular methods, high-throughput screens, and biophysical and computational models, has revealed further aspects of this flow and how polarity regulators respond to and modulate it. Here, we review recent findings on the interplay between actomyosin flow and the PAR patterning networks in the polarization of the C. elegans zygote. We also discuss how these discoveries and developed methods are shaping our understanding of other flow-dependent polarizing systems. This article is part of a discussion meeting issue ‘Contemporary morphogenesis’.

RalA is a small GTPase and a member of the Ras family. This molecular switch is activated downstream of Ras and is widely implicated in tumor formation and growth. Previous work has shown that the ubiquitous Ca2+-sensor calmodulin (CaM) binds to small GTPases such as RalA and K-Ras4B, but a lack of structural information has obscured the functional consequences of these interactions. Here, we have investigated the binding of CaM to RalA and found that CaM interacts exclusively with the C terminus of RalA, which is lipidated with a prenyl group in vivo to aid membrane attachment. Biophysical and structural analyses show that the two RalA membrane-targeting motifs (the prenyl anchor and the polybasic motif) are engaged by distinct lobes of CaM and that CaM binding leads to removal of RalA from its membrane environment. The structure of this complex, along with a biophysical investigation into membrane removal, provides a framework with which to understand how CaM regulates the function of RalA and sheds light on the interaction of CaM with other small GTPases, including K-Ras4B.

As in mammals, only one cell in a Drosophila multicellular female germline cyst is specified as an oocyte. The symmetry-breaking cue for oocyte selection is provided by the fusome, a tubular structure connecting all cells in the cyst. The Drosophila spectraplakin Shot localises to the fusome and translates its asymmetry into a polarised microtubule network that is essential for oocyte specification, but how Shot recognises the fusome is unclear. Here we demonstrate that Shot's actin-binding domain (ABD) is necessary and sufficient to localise Shot to the fusome and mediates Shot function in oocyte specification together with the microtubule-binding domains. The calponin homology domain 1 of Shot's ABD recognises fusomal F-actin and distinguishes it from other forms of F-actin in the cyst. By contrast, the ABDs of Utrophin, Fimbrin, Filamin, as well as Lifeact and F-tractin do not recognise fusomal F-actin. We therefore propose that Shot propagates fusome asymmetry by recognising a specific conformational state of F-actin on the fusome.