@article {69148, title = {Bridging gaps in traditional research training with iBiology Courses.}, journal = {PLoS Biology}, volume = {22}, year = {2024}, month = {2024 Jan 11}, pages = {e3002458}, abstract = {

iBiology Courses provide trainees with just-in-time learning resources to become effective researchers. These courses can help scientists build core research skills, plan their research projects and careers, and learn from scientists with diverse backgrounds.

}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3002458}, author = {Schnoes, Alexandra M and Green, Noah H and Nguyen, Thi A and Vale, Ronald D and Goodwin, Sarah S and Behrman, Shannon L} } @article {69170, title = {Mechanical stretch regulates macropinocytosis in Hydra vulgaris.}, journal = {Molecular Biology of the Cell}, year = {2024}, month = {2024 Jan 24}, pages = {mbcE22020065}, abstract = {

Cells rely on a diverse array of engulfment processes to sense, exploit, and adapt to their environments. Among these, macropinocytosis enables indiscriminate and rapid uptake of large volumes of fluid and membrane, rendering it a highly versatile engulfment strategy. Much of the molecular machinery required for macropinocytosis has been well established, yet how this process is regulated in the context of organs and organisms remains poorly understood. Here, we report the discovery of extensive macropinocytosis in the outer epithelium of the cnidarian . Exploiting {\textquoteright}s relatively simple body plan, we developed approaches to visualize macropinocytosis over extended periods of time, revealing constitutive engulfment across the entire body axis. We show that the direct application of planar stretch leads to calcium influx and the inhibition of macropinocytosis. Finally, we establish a role for stretch-activated channels in inhibiting this process. Together, our approaches provide a platform for the mechanistic dissection of constitutive macropinocytosis in physiological contexts and highlight a potential role for macropinocytosis in responding to cell surface tension. [Media: see text] [Media: see text] [Media: see text] [Media: see text].

}, issn = {1939-4586}, doi = {10.1091/mbc.E22-02-0065}, author = {Skokan, Taylor D and Hobmayer, Bert and McKinley, Kara L and Vale, Ronald D} } @article {68562, title = {In situ cryo-electron tomography reveals the asymmetric architecture of mammalian sperm axonemes.}, journal = {Nature Structural \& Molecular Biology}, volume = {30}, year = {2023}, month = {2023 Mar 01}, pages = {360-9}, abstract = {

The flagella of mammalian sperm display non-planar, asymmetric beating, in contrast to the planar, symmetric beating of flagella from sea urchin sperm and unicellular organisms. The molecular basis of this difference is unclear. Here, we perform in situ cryo-electron tomography of mouse and human sperm, providing the highest-resolution structural information to date. Our subtomogram averages reveal mammalian sperm-specific protein complexes within the microtubules, the radial spokes and nexin-dynein regulatory complexes. The locations and structures of these complexes suggest potential roles in enhancing the mechanical strength of mammalian sperm axonemes and regulating dynein-based axonemal bending. Intriguingly, we find that each of the nine outer microtubule doublets is decorated with a distinct combination of sperm-specific complexes. We propose that this asymmetric distribution of proteins differentially regulates the sliding of each microtubule doublet and may underlie the asymmetric beating of mammalian sperm.

}, issn = {1545-9985}, doi = {10.1038/s41594-022-00861-0}, author = {Chen, Zhen and Greenan, Garrett A and Shiozaki, Momoko and Liu, Yanxin and Skinner, Will M and Zhao, Xiaowei and Zhao, Shumei and Yan, Rui and Yu, Zhiheng and Lishko, Polina V and Agard, David A and Vale, Ronald D} } @article {65898, title = {Structure of the radial spoke head and insights into its role in mechanoregulation of ciliary beating.}, journal = {Nature Structural Molecular Biology}, volume = {28}, year = {2020}, month = {2020 Dec 14}, pages = {20-28}, abstract = {

Motile cilia power cell locomotion and drive extracellular fluid flow by propagating bending waves from their base to tip. The coordinated bending of cilia requires mechanoregulation by the radial spoke (RS) protein complexes and the microtubule central pair (CP). Despite their importance for ciliary motility across eukaryotes, the molecular function of the RSs is unknown. Here, we reconstituted the Chlamydomonas reinhardtii RS head that abuts the CP and determined its structure using single-particle cryo-EM to 3.1-{\r A} resolution, revealing a flat, negatively charged surface supported by a rigid core of tightly intertwined proteins. Mutations in this core, corresponding to those involved in human ciliopathies, compromised the stability of the recombinant complex, providing a molecular basis for disease. Partially reversing the negative charge on the RS surface impaired motility in C. reinhardtii. We propose that the RS-head architecture is well-suited for mechanoregulation of ciliary beating through physical collisions with the CP.

}, issn = {1545-9985}, doi = {10.1038/s41594-020-00519-9}, author = {Grossman-Haham, Iris and Coudray, Nicolas and Yu, Zanlin and Wang, Feng and Zhang, Nan and Bhabha, Gira and Vale, Ronald D} }