#podosomes

Show Your Teeth

Phagocytes are immune cells with a big appetite. They usually engulf whole pathogens, but this phagocyte has been fooled – placed over a glass plate loaded with tempting antibodies it stretches out over something it can never consume. This ‘frustrated’ phagocytosis allows researchers to peek at the molecular machinery involved, poking a microscope into the opening 'jaw' of a phagocyte. A technique called iPALM highlights its skeleton of tiny actin filaments that rearrange to form rings of pointy structures called podosomes – sometimes known as phagocytic teeth – used to latch onto targets at the beginning of phagocytosis. Rainbow colours highlight actin fibres at different depths, giving researchers hints to the 3D structure of podosomes, that future drug treatments may influence to improve the fight against disease-carrying pathogens.

Written by John Ankers

Image from work by J. Cody Herron, Shiqiong Hu and Takashi Watanabe, and colleagues

University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, July 2022

Nanoscale Remodelling

Remodelling is complicated, whether it's your house or your bones. Bone remodelling happens when your bones are damaged, whether that's a fracture or everyday strain. Cells called osteoclasts jump into action to break down old bone so new bone can form. Anchoring themselves to the bone, they form a ring-like structure called the sealing zone, into which bone-degrading substances are released without leaking away. Projections made of actin – podosomes – help form the sealing zone, but their organisation at the nanoscale level is unclear. Researchers use super-resolution microscopy to investigate. Human osteoclasts, containing fluorescently tagged actin, were live imaged adhering to bone (pictured). This revealed densely packed actin cores, which form the centre of podosomes, in the sealing zone. Further analysis revealed the activity of these cores was synchronised locally, with groups of cores surrounded by adhesion proteins. This shines a light on the nanoscale lives of podosomes in bone remodelling.

Written by Lux Fatimathas

Video from work by Marion Portes and colleagues

Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, June 2022

Around the Bend

Cells rely on a flexible skeleton of tiny actin filaments, prodding into the cellular floor like tent poles anchored in the living environment around them. Here they’re revealed – virtually sifted out like treasure trove from sand using a technique called electron cryotomography. The actin fibres in this human cell are highlighted in rainbow colours based on their orientation towards the floor. They form a dense stack alongside other fibres (brown) nestling below the cell’s organelles (grey) in cell regions called podosomes. With help from mathematical modelling, researchers find the complex mesh of fibres pulls together to store large amounts of elastic energy in the central core of bending actin fibres – like coiled springs they punch out, helping the cell to feel grip or destroy the surrounding environment. These models used may now be adapted to investigate forces in other cells, perhaps during development or during the spread of cancer.

Written by John Ankers

Video from work by Marion Jasnin and colleagues

Max Planck Institute of Biochemistry, Martinsried, Germany; Université de Paris, CNRS, Institut Jacques Monod, Paris and Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, France

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, July 2022