Investigating protrudin’s role in neuroprotection and axon regeneration in the central nervous system

Protrudin — a transmembrane scaffold protein found in tubular regions of the endoplasmic reticulum (ER) — has previously been shown to strongly promote neuronal survival and axon regeneration after central nervous system (CNS) injury. This is in part due to increased levels of integrins in the distal axon, but this mechanism does not fully account for its beneficial effects. We have investigated protrudin's effects on intracellular transport, morphology, and protein localisation in neurons, and found varied but specific effects on different cellular systems. In particular, protrudin does not have any effect on the transport of late endosomes in CNS neurons — despite evidence for this mechanism in other cell types — due to the absence of key adaptor protein FYCO1 in mature neurons. It also does not have any substantial effect on dendritic spine morphology, so it does not indiscriminately promote cellular outgrowth. On the other hand, protrudin does interact with ER export and associated secretory machinery. Overexpression of an active mutant of protrudin increases the amount of an ER-Golgi intermediate compartment in axon terminals, and affects the transport of Golgi satellite organelles, which we observed even in the distal axon. Our data demonstrates that protrudin provides axons with the machinery for local membrane protein synthesis, which may play a role in neuron survival and regeneration. This work opens up new avenues for future research into adult CNS repair.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2023

Author dc:creator

• Love, Fiona

Advisor dc:contributor.advisor

• Eva, Richard

• axon regeneration
• cell biology
• gene therapy
• glaucoma
• neuroscience

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/8f56a319-ecc4-4750-bef7-eaabe0864381/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

Author Identifier

0000-0002-7805-5234

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/362643