#clathrin

In the Pits

Cells don’t always have everything they need in-house. So, they receive deliveries including metabolites, hormones and proteins from elsewhere. This cargo is taken up via a process called clathrin-mediated endocytosis. Pits coated in the structural protein clathrin form on the surface of a cell’s membrane to collect the required goods and then pinch off into sacs. Here, researchers investigate the 'machinery' underpinning this operation, focusing on the protein CCDC32, which interacts with the clathrin coating and is mutated in the congenital disease cardio-facio-neuro-developmental syndrome. Using a type of electron microscopy (PREM) that 'unroofs' the clathrin-coated structures, they showed that in cells with reduced amounts of CCDC32 (pictured, right), there were fewer dome- (green) and spherical-shaped (orange) pits and more flat, clathrin-coated structures (blue) compared to normal cells (left). They also revealed the disease-causing mutant of CCDC32 prevents endocytosis in cells grown in a dish, so confirming a key role for CCDC32 in this cellular uptake process.

Written by Lux Fatimathas

Image from work by Ziyan Yang and colleagues

NHC Key Laboratory of Birth Defect Research and Prevention,Hengyang Medical School, University of South China, Hengyang, China; Chan Zuckerberg Biohub, San Francisco, CA, USA

Video contributed by the authors and originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife (reviewed preprint), August 2025

エンドサイトーシス関連の分子クラスリン（緑色）とアクチン（赤色）の相互作用を捉えたSIM（構造化照明顕微鏡）映像です。

エンドサイトーシス（細胞膜内への取り込み）の1種であるクラスリン依存性エンドサイトーシスに必須なクラスリン分子をmEmerald-clathrinで可視化、アクチンをmCherry-Lifeactで可視化しています。

Intracellular distribution of epsin 1. (A Upper) Immunofluorescence image of endogenous epsin 1 (red) and endogenous clathrin (green). (Lower) Magnified view of the boxed region. Shown are the epsin 1(Left), clathrin (Center), and overlaid (Right) images. (B Upper) Overlay of the Venus fluorescence image of epsin 1-Venus (green) and the immunofluorescence image of endogenous clathrin (red). The cell was transiently transfected with epsin 1-Venus. (Lower) Magnified view of the boxed region. Shown are the epsin 1-Venus (Left), clathrin (Center), and overlaid (Right) images. (Scale bars,10 μm.)

Arrestin: recruited

Scientists solve decades-old cell biology puzzle

Researchers at EMBL Heidelberg have solved a question that has puzzled cell biologists for decades – how does the protein machine that allows cells to swallow up molecules during endocytosis function?

In the first model, the clathrin lattice, or coat, first assembles as a flat structure, and then bends, essentially wrapping around the forming vesicle. In the second model, scientists suggest that clathrin assembles directly, assuming the shape of the membrane as it is drawn inwards.

Although the second model has been more generally accepted, a new paper published today in Science, shows that, in fact, the first explanation is more accurate. In their experiments, the team at EMBL Heidelberg used human cell lines in which the sites where endocytosis was taking place had been tagged with a fluorescent marker.EMBL post-doctoral researcher, Ori Avinoam, then used 3D electron microscopy to take pictures of these sites and analysed them to understand how they changed shape over time.

By analysing the images computationally, the research team was able to demonstrate that the surface area of the clathrin coat does not change during endocytosis, only its curvature changes as it draws the cell membrane inwards.

More information: "Endocytic sites mature by continuous bending and remodeling of the clathrin coat" Science 19 June 2015:  Vol. 348 no. 6241 pp. 1369-1372 DOI: 10.1126/science.aaa9555

New measures call theories about endocytosis into question

Cellular biology still harbors mysteries. Notably, there is no unequivocal explanation behind endocytosis, the biological process that allows exchanges between a cell and its environment. Two hypotheses prevail for explaining how the wall caves in and forms transport vesicles: either the initial impetus is due to a scaffold-like structure which the soccer ball-shaped clathrin proteins build between themselves, or clathrin's role is minor, and it is other, «adaptor" proteins who exert pressure on the cell wall until endocytosis begins. One recently completed study by the Faculty of Science at the University of Geneva (UNIGE) reconciles the two theories, suggesting a balance between forces present: clathrin proteins are only slightly more influential than the others, and it is a clever combination of physical mechanisms that contributes to creating favorable conditions for the deformation of the membrane. These conclusions captured the interest of the editors of Nature Communications, who just published them.