Sophisticated imaging exposes elaborate cell transport system
Intracellular transport – the internal movement of cell components along myriad pathways – is incredibly complex, dynamic and difficult to observe using traditional imaging approaches. Now a team at Monash Biomedicine Discovery Institute has illuminated a vital part of this process.
These findings were published in Communications Biology today.
Dr Senthil Arumugam, who heads the Cellular Physiology Lab, has used sophisticated technology at Monash University to describe a novel ‘priority-shipping’ process for epidermal growth factor receptors (EGFR). Growth factor receptors help cells make important decisions such as whether to move or to proliferate. The endosomal transport of these receptors goes awry in many forms of cancer and can underpin chemotherapy resistance.
How epidermal growth factor receptors are managed within the transport network is poorly understood.
Dr Arumugam and his team used Lattice Light-Sheet Microscopy (LLSM) to reveal a pivotal part of the process. Monash University is one of a few institutions in Australia to acquire the technology, developed by Nobel laureate Professor Eric Betzig.
Dr Arumugam likens intracellular transport to the way a city is organised. A city’s public transport system consists of buses, light rails, and specific highways for long distance transport; the inside of cells contains tracks of varying lengths comprised of self-assembled, polymerised proteins. Along these tracks travel membrane vesicles, also known as endosomes, that carry specific cargoes. These transport carriers are pulled by motor proteins that generate the force to pull the membrane vesicles to move along the tracks, much like the engines in vehicles.
Endosomal transport has been difficult to image because the endosomes are tiny – typically about 0.1 to 1 micrometre or up to 1000 times smaller than the thickness of human hair – and move fast.
To image such rapid events with a high level of detail, whilst capturing large volumes, requires sophisticated technologies. Lattice Light-Sheet Microscopy allows imaging with high-resolution of large whole-cell volumes in space and time with minimised light-induced damage to living samples.
“Using LLSM, we observed that upon growth factor stimulation, the cellular transport network is re-configured transiently to execute a cohort, rapid transport of all EGFRs from the boundary of the cell to the centre of the cell,” Dr Arumugam said.
“This is significant to understand how cells ‘interpret’ signals as a fundamental question as well as to better understand the role of EGFR signalling in cancer cell biology,” he said.
“The ability of LLSM to tackle fast imaging of volumes was indispensable to discover this whole-cell spanning process that integrates biochemical events, calcium currents, and rapid transport.”
The lab has also been focusing on understanding this endosomal transport machinery in the contexts of fundamental processes central to a living celland A-beta pathophysiology in Alzheimer’sdisease.
The BDI’s PhD student, Harrison York, was first author on the paper along with fellow PhD students in the lab Abhishek Patil and Ullhas K. Moorthi, who made significant contributions to the study.
Read the full paper in Communications Biology titled: Rapid Whole Cell Imaging Reveals An APPL1-Dynein Nexus That Regulates Stimulated EGFR Trafficking
DOI: 10.1038/s42003-021-01740-y
About the Monash Biomedicine Discovery Institute at Monash University
Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Spanning six discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection and Immunity, Metabolic Disease and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.
For media enquiries please contact:
Monash University Media
Wendy Smith - Media and Communications
Tel: +61 (0) 425 725 836
E: wendy.smith1@monash.edu