#endosomes

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Traffic and Travel

Carrying messages to and from our moving limbs, neurons rely on signalling endosomes to ferry supportive chemicals along their branches or axons. Although ten million times smaller than postable parcels, here researchers use intravital imaging to capture a bustling traffic of endosomes (highlighted in blue) shuttling through a mouse’s sciatic nerve. The technique involves anaesthetising the mouse and exposing its nerve under a microscope – it reveals endosomes carrying BDNF, a type of neurotrophin which helps to keep neurons healthy. Certain genetic mutations can block BDNF traffic at junctions where nerve meets muscle, leading to weakness or muscle wasting. The team hopes designing drugs to boost BDNF may restore endosome transport and bring relief to human patients with disorders like Charcot-Marie-Tooth disease.

Written by John Ankers

Video from work by James N. Sleigh and colleagues

Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London, UK

Video copyright held by James N. Sleigh

Research published in JCI Insight, March 2023

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In the Endosome

Greater understanding of G-protein signalling – molecular programs involving cell organelles called endosomes that regulate physiological processes throughout the body such as water re-absorption via the kidney

Read the published research paper here

Image from work by Carole Daly and colleagues

Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK

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

Published in eLife, October 2023

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Disrupted Delivery

Inside each cell, a fleet of delivery vehicles ferry packages from A to B, ensuring proteins and nutrients are efficiently deposited where they are needed most. Any malfunction of these transporters, called endosomes, can cause traffic jams and protein pileups. WASHC4 (green in the mouse brain section pictured) is a protein involved in endosome trafficking, and previous research has shown that children with a genetic mutation affecting this protein have trouble learning. To investigate, researchers replicated this mutation in mice. The mice developed fewer WASHC4 proteins, oversized endosomes, and an excess of proteins that break down material, causing a build up of debris. The mice with this disrupted delivery system showed learning difficulties and developed movement problems that worsened with age, also found in patients with the mutation. Understanding the molecular basis for the physical symptoms could lead to new approaches to treatment or, even better, prevention.

Written by Anthony Lewis

Image from work by Jamie L Courtland and Tyler WA Bradshaw, and colleagues

Duke University School of Medicine, Durham, NC, USA

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

Published in eLife, March 2021

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Feeling Lowe

Also known as oculocerebrorenal syndrome, Lowe syndrome is a rare genetic disorder that causes a range of eye, kidney and brain problems such as seizures. It’s due to faults in a gene called OCRL, but until now it’s been unclear exactly what the gene does or why the faulty version causes such diverse symptoms. By studying the equivalent gene in fruit flies, scientists have discovered that OCRL is involved in making and moving tiny molecular packages inside cells, known as endosomes. This time-lapse projection shows the endosomes in healthy fruit fly immune cells, with each one digitally coded with a different colour and followed for just four minutes. Without OCRL, the immune cells are activated when they shouldn’t be, releasing their endosomes and causing inflammation. If the same thing happens in human cells, inflammation in the brain might explain the seizures and other symptoms seen in children with Lowe syndrome.

Today is Rare Disease Day

Written by Kat Arney

Image by Steven Del Signore, Brandeis University

Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA, USA

Image originally published under a Creative Commons Licence (BY 4.0)

Research published in PLOS Genetics, October 2017

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[kamalkafir-blog]

EndoMAP.v1 charts the structural landscape of human early endosome complexes

Reagents The following chemicals and reagents were used: Dounce homogenizer (DWK Life Sciences, 885302-0002); Pierce anti-HA magnetic beads (Thermo Scientific, 88837); Pierce anti-Flag magnetic agarose (Thermo Scientific, A36797); anti-Flag M2 magnetic beads (Sigma Millipore, M8823); Pierce protein A/G magnetic beads (Thermo Scientific, 88802); IGEPAL CA-630 (Sigma-Aldrich, I8896); S-Trap micro…

[whats-in-a-sentence]

The ER exit sites are determined by the presence of a coat protein called COPII (see Figure 1.16A). (...) The trans cisternae then "fall off" the stack and form the trans Golgi network, which then produces secretory vesicles (see Figure 1.16A).

The small (100 nm) vesicles are initially coated with clathrin (see Figure 1.16), but they quickly lose that coat and fuse with other tubules and vesicles; the organelles of this endocytic pathway are called endosomes.

The endosome can then be targeted either back to the trans Golgi network for secretion or to a structure called the prevacuolar compartment for hydrolytic degradation (see Figure 1.16A). (...) Those vacuoles that do receive Golgi-derived vesicles do so via an intermediate, prevacuolar compartment that also serves as a sorting organelle for membrane endocytosed from the plasma membrane (see Figure 1.16A).

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[currentsinbiology]

The ups and downs of transportation within cells

How do cells avoid growing topsy-turvy?  Growing so your top, front, bottom and back all wind up on the correct side requires a good sense of direction at the cellular level.  A Hiroshima University research group has identified a familiar gene with an unexpected role in directing proteins around the cell. 

"The Golgi Body is like a logics center of the cell.  Proteins move forward through it like a factory until they reach the distribution centers, which are called the Trans Golgi Network and the Recycling Endosome.  We discovered a gene called Rab6 is involved in distinguishing between proteins that can go directly to specific sides of the cell from the Trans Golgi Network and proteins that need to move into the Recycling Endosome before being transported," said Takunori Sato, PhD, a collaborator in Akiko K. Sato's laboratory.

Caption:Transmission electron microscope images of healthy fruit fly eyes (left) and flies with no Rab6 (right).  Purple highlight shows the normal space between parts of cells and blue highlight shows the collection of multi-vesicular bodies containing proteins that have been shipped incorrectly from the Golgi body. Image by Yuri Nakamura, Hiroshima University.

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Golden Opportunity

The debilitating side-effects of chemotherapy are largely a result of delivering drugs via the bloodstream. This 'whole-body' approach means chemotherapy kills actively dividing cancer cells, but also damages non-malignant tissue – leading to hair loss, hearing damage and nausea. The ability to directly target tumour cells, while sparing healthy tissue, might reduce side-effects and enable larger doses of drug to be used. Scientists at Imperial College London have been experimenting with non-toxic gold nanoparticles (red), just a few billionths of a metre across, that can be inhaled, and so delivered directly to cancer cells in the lung (nucleus stained blue). These particles are coated with chemotherapy drugs, which are taken up by the cells’ active transport system, or endosomes (green). Additionally, the particles can be heated with infrared radiation, and this helps to kill cancer cells. Initial results from cells in culture are encouraging, and the team now plans pre-clinical trials.

Find out more about this study.

Written by Jake Jacobson

Image from work by Andrew Thorley and colleagues

National Heart and Lung Institute at Imperial College London, UK

Image copyright held by original authors

Research presented at the British Thoracic Society Winter Meeting, December 2015

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