Year-end Sale % OFF 
Abstract
Polarity, which refers to the molecular or structural asymmetry in cells, is essential for diverse cellular functions. Dictyostelium has proven to be a valuable system for dissecting the molecular mechanisms of cell polarity. Previous studies in Dictyostelium have revealed a range of signaling and cytoskeletal proteins that function at the leading edge to promote pseudopod extension and migration. In contrast, how proteins are localized to the trailing edge is not well understood. By screening for asymmetrically localized proteins, we identified a novel trailing-edge protein we named Teep1. We show that a charged surface formed by two pleckstrin homology (PH) domains in Teep1 is necessary and sufficient for targeting it to the rear of cells. Combining biochemical and imaging analyses, we demonstrate that Teep1 interacts preferentially with PI(4,5)P2 and PI(3,5)P2 in vitro and simultaneous elimination of these lipid species in cells blocks the membrane association of Teep1. Furthermore, a leading-edge localized myotubularin phosphatase likely mediates the removal of PI(3,5)P2 from the front, as well as the formation of a back-to-front gradient of PI(3,5)P2. Together our data indicate that PI(4,5)P2 and PI(3,5)P2 on the plasma membrane jointly participate in shaping the back state of Dictyostelium cells.
Highlights
Dynamic anterior-posterior polarity is a hallmark of eukaryotic motile cells
We focused on pleckstrin homology (PH) domain-containing proteins because of their known functions in phosphoinositide signaling and polarity regulation
When the Latrunculin A (LatA)-treated cells were exposed to a cAMP gradient, Teep1 exhibited a complementary distribution to PHcrac, forming a crescent away from the higher concentration of cAMP (Supplementary Figure S2B)
Summary
Dynamic anterior-posterior polarity is a hallmark of eukaryotic motile cells. Cell polarity can be organized spontaneously or under the guidance of extracellular biochemical and mechanical cues (Goehring and Grill, 2013; Campanale et al, 2017). Study of cell migration in the model system Dictyostelium discoideum has provided important insights into the mechanisms underlying the establishment and maintenance of cell polarity (King and Insall, 2009; Devreotes et al, 2017). Many key signaling or cytoskeletal molecules involved in polarity regulation were originally discovered in Dictyostelium and later found to be conserved in higher eukaryotic cells. In Dictyostelium, signaling and cytoskeletal components responsible for polarity regulation are often localized or activated at the leading edge (front) or trailing edge (back) of migrating cells, creating functionally distinct ends that promote cell migration. Events that occur at the leading edge include the activation of several Ras and Rac family GTPases, activation of mTORC2 and its substrates of the Akt/PKB family kinases, accumulation of the class I PI3-kinases (PI3Ks) and their product PIP3, and recruitment of a number of regulators of actin polymerization, such as the Scar/ WAVE and Arp2/3 complexes responsible for pseudopod projection
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
