Journal of Cell Biology最新文献

BAR domain-containing proteins are key regulators of endocytosis and actin remodeling. Their function in morphogenesis remains to be investigated. We report that the I-BAR domain-containing protein, missing-in-metastasis (MIM) (also called MTSS1), promotes branched actin network formation and endocytosis to drive rapid, cyclical plasma membrane remodeling during syncytial divisions in Drosophila embryos. Actin-rich villous protrusions in the apical caps in interphase are depleted in metaphase, concurrent with furrow extension between adjacent nuclei. MIM depletion results in a loss of furrow extension and in longer, more abundant apical protrusions containing the formin diaphanous. Branched actin networks promoted by MIM are in balance with bundled actin networks induced by RhoGEF2 and diaphanous. Cyclical recruitment of MIM to the cortex promotes localization of active Rac, the WAVE regulatory complex, and the Arp2/3 complex to drive endocytic membrane remodeling. These findings identify MIM as an integrator of actin and endocytic dynamics that enables rapid membrane remodeling during Drosophila syncytial division cycles.

Collective chemotaxis is often viewed through a mesenchymal lens, emphasizing peripheral polarity and force generation. In this issue, Diaz and Mayor (https://doi.org/10.1083/jcb.202507211) reveal that epithelial-like neural crest clusters achieve directed chemotaxis through a junction-centered strategy that redistributes polarity, contractility, and traction forces internally.

Epithelial tissues are populated with accessory cells including pigment-producing melanocytes, which must migrate between tightly adherent epithelial cells, but how cells migrate through confined epithelial spaces without impairing barrier function is poorly understood. Using live imaging of the mouse epidermis, we captured the migration of embryonic melanocytes (melanoblasts) while simultaneously visualizing the basement membrane or epithelial surfaces. We show that melanoblasts migrate through basal and suprabasal layers of the epidermis where they use keratinocyte surfaces, as well as the basement membrane, as substrates for migration. Melanoblasts form atypical and dynamic E-cadherin attachments to keratinocytes that largely lack cytoplasmic catenins known to anchor E-cadherin to F-actin. We show E-cadherin is needed in both melanoblasts and keratinocytes to stabilize migratory protrusions, and that depleting E-cadherin results in reduced melanoblast motility and ventral depigmentation in adult mice. These findings illustrate how migratory cells modify the cell adhesion machinery to invade between connected epithelial cells without interrupting the skin barrier.

Lipid bilayers form the basis of organellar architecture, structure, and compartmentalization in the cell. Decades of biophysical, biochemical, and imaging studies on purified or in vitro-reconstituted liposomes have shown that variations in lipid composition influence the physical properties of membranes, such as thickness and curvature. However, similar studies characterizing these membrane properties within the native cellular context have remained technically challenging. Recent advancements in cellular cryo-electron tomography (cryo-ET) imaging enable high-resolution, three-dimensional views of native organellar membrane architecture preserved in near-native conditions. We previously developed a "Surface Morphometrics" pipeline that generates surface mesh reconstructions to model and quantify cellular membrane ultrastructure from cryo-ET data. Here, we expand this pipeline to measure the distance between the phospholipid head groups of the membrane bilayer as a readout of membrane thickness. Using this approach, we demonstrate thickness variations both within and between distinct organellar membranes. We show that organellar membrane thickness positively correlates with other features, such as membrane curvedness, in cells. Further, we show that subcompartments of the mitochondrial inner membrane exhibit varying membrane thicknesses that are independent of whether the mitochondria are in fragmented or elongated networks. We also demonstrate that our technique, when applied to three-dimensional data, yields results that match existing measurements obtained from two-dimensional data of in vitro samples. Finally, we demonstrate that large membrane-associated macromolecular complexes exhibit distinct density profiles that correlate with local variations in membrane thickness. Overall, our updated Surface Morphometrics pipeline provides a framework for investigating how changes in membrane composition in various cellular and disease contexts affect organelle ultrastructure and function.

Lipid droplets (LDs), originating from the ER, play critical roles in lipid metabolism. ER-LD contacts enable lipid exchange and support essential cellular processes. However, how viruses utilize ER-LD coordination remains elusive. Here, we demonstrate that hepatitis C virus (HCV) infection markedly increases LDs abundance and enhances ER-LD contacts. Through a targeted screen of ER-LD tethering proteins, we identified that the NRZ complex, composed of nonsteroidal anti-inflammatory drug-activated gene (NAG), RAD50 interactor 1 (RINT1) and zeste white 10 (ZW10), is essential for HCV-induced ER-LD association and viral infection. Mechanistically, RINT1 and ZW10 interact with the HCV envelope protein E1. Ectopic E1 expression is sufficient to promote ER-LD contacts, which are abolished upon NRZ depletion. NRZ depletion also impairs Dengue virus (DENV) and Zika virus (ZIKV) infection, suggesting its conserved proviral function. Together, this work uncovers a critical mechanism by which host inter-organelle tethering complexes regulate viral infection, offering new insights into virus-host interactions and potential antiviral targets.

Abl-interactor (Abi) proteins induce actin polymerization by activating Wiskott-Aldrich syndrome protein (WASp) or SCAR/WASP-family verprolin-homologous protein. Loss of mammalian Abi1 causes myeloproliferative neoplasm; however, little is known about how the Abi family of actin-regulatory proteins regulates blood cell homeostasis. Here, we demonstrate that Drosophila Abi promotes plasmatocyte-to-crystal cell transdifferentiation but represses plasmatocyte-to-lamellocyte transdifferentiation through Notch signaling. Consistent with a previously demonstrated role of clathrin-mediated endocytosis (CME) in Notch signaling activation, we find that Abi promotes Notch-CME by recruiting WASp and the Notch receptor to nascent sites of CME. Finally, we demonstrate that CME and crystal cell formation are inhibited by Abelson (Abl)-mediated phosphorylation of Abi but require PTP61F, a phosphatase that reverses this phosphorylation. Our findings identify Abi as a critical integrator of actin remodeling and Notch-CME and reveal opposing roles of Abl and PTP61F in regulating Abi activity to maintain blood cell homeostasis.

In this issue, Almasoud et al. (https://doi.org/10.1083/jcb.202504139) report a surprising finding that epithelial cell polarity is present in a tissue with no known polarized function, in a cell type that was assumed to show a distinct lack of such polarity-the mesenchymal cells of the Drosophila fat body. Exceptions such as this help to broaden our understanding of the use of regulators and pathways we thought we fully understood.

Interactions between actin filaments and microtubules (MTs) are essential, but how those mechanisms are orchestrated in complex developing systems is poorly understood. Here we show that actin-MT cross talk regulates actin cable assembly and the assembly and organization of MTs in Drosophila nurse cells during oogenesis. We found that a stable, acetylated MT meshwork develops concurrently with actin cable initiation and requires acetylation for its maintenance. These γ-tubulin-nucleated MTs appear to be cortically tethered via Patronin and Shortstop, extend into the cytoplasm, and coalign with the elongating actin cables. We showed that this MT network is required for actin cable initiation and elongation. We further demonstrated that actin filament assembly via Diaphanous and Enabled promotes cortical tethering of MTs and that loss of the actin filament bundlers Quail/Villin, Singed/Fascin, and Fimbrin resulted in fewer, shorter, and more highly coaligned MTs. Together, our data reveal multiple modes of coordinated actin-MT cross talk that are instrumental for oogenesis.