Holes in the plasma membrane trigger the activation of the Torso receptor tyrosine kinase.
As a general rule, cells don’t do well when holes are poked in their plasma membranes. That’s why many immune cells use enzymes like perforin to puncture the membranes of pathogenic cells, dysregulating and often killing them. However, a new report in GENETICS by Mineo et al. suggests that creating holes in the plasma membrane might be a normal and necessary process during development.
The authors were interested in whether membrane hole-punching could play a role in activation of a receptor tyrosine kinase known as Torso. Torso is crucial for development of the fruit fly Drosophila melanogaster and is activated at both poles of the developing embryo. Torso activation depends on the polar accumulation of Torso-like (Tsl), which is the only Drosophila protein known to have a Membrane Attack Complex/Perforin domain. This domain is often present in proteins that perforate cell membranes, so the authors hypothesized that Tsl’s function might be to create membrane pores and, therefore, that simply pricking holes in the cell membrane might substitute for its function.
To test their hypothesis, Mineo et al. studied mutant embryos that either lacked the Tsl protein entirely or carried a non-functional version; both mutants exhibit several easily observable developmental defects. At this stage of development, the embryos are syncytial, which means all the dividing nuclei share a common cytoplasm and are surrounded by a single cell membrane. The researchers poked holes in the membrane at the poles of the embryo using sharpened capillaries of the type sometimes used to inject DNA for genetic engineering. Remarkably, embryos that had holes poked in them had fewer defects than their un-poked counterparts, suggesting that the mechanical formation of holes partially compensate for Tsl function.
To determine whether the rescue was due to mechanical stress on the membrane—but not necessarily the holes themselves—the authors then prodded membranes but did not puncture them. Prodded embryos showed the same developmental defects as their untreated counterparts, showing that an actual rupture in the membrane was required to rescue the developmental phenotype in Tsl-deficient fly embryos.
The authors also demonstrated that Torso signaling is required for the rescue effect of these membrane holes; fly embryos lacking Torso or its ligand, Trunk, did not show any change in developmental phenotypes when they were mechanically punctured. The location of the holes also mattered; the rescue was greatly diminished when the holes were created in the middle of the embryos, rather than at their poles.
Overall, the results suggest that Tsl spatiotemporally regulates Torso signaling by puncturing the cell membrane. These punctures are presumably needed for the exchange of a molecular signal between the interior of the embryo and its extracellular surroundings; it remains to be seen exactly how activation by Tsl works. What is clear is that, sometimes, all that’s needed to keep development on track is a sharp punch in the membrane.
CITATION:
Holes in the Plasma Membrane Mimic Torso-Like Perforin in Torso Tyrosine Kinase Receptor Activation in the Drosophila Embryo
Alessandro Mineo, Esther Fuentes, Marc Furriols, Jordi Casanova
; https://doi.org/10.1534/genetics.118.301397
http://www.genetics.org/content/210/1/257
Science Writing and Communications Intern, Genetics Society of America.
View all posts by Marisa Wexler »Read more in
-
In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation
Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…
-
Congratulations to the #Fungal24 Poster Award winners!
We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…
-
Poster presentation tips for TAGC 2024
You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…
-
Maximize your TAGC 2024 experience
A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…
-
Early Career Leadership Spotlight: Sarah Petrosky
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…
-
TAGC 2024 Early Career Award Winners
GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024. Don’t miss the opportunity…
-
Preeminent geneticists recognized with revamped GSA Awards
In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…
-
Fly Board funds outreach programs to spread the word about Drosophila research
In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…
-
New members of the GSA Board of Directors: 2024–2026
We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…
-
Parrot plumage study aids breeders and endangered natural populations
Yellow coloration is maladaptive in the wild but prized by breeders. People have long been fascinated with birds, which exhibit one of the widest ranges of coloration among vertebrates. Parrots, in particular, have captivated humans by their ability to mimic human speech and spectacular plumage. Brightly colored feathers are used primarily to attract mates, intimidate…
-
Early Career Leadership Spotlight: Sarah Gilmour
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah GilmourMultimedia SubcommitteeStowers Institute for Medical Research Research Interest Questions of evolution have always fascinated me. I am extremely fortunate to be starting out my research career in a…