The cellular uptake of angiogenin, an angiogenic and neurotrophic factor is through multiple pathways and largely dynamin independent

Ross Ferguson, Vasanta Subramanian

Research output: Contribution to journalArticle

Abstract

Angiogenin (ANG), a member of the RNase superfamily (also known as RNase 5) has neurotrophic, neuroprotective and angiogenic activities. Recently it has also been shown to be important in stem cell homeostasis. Mutations in ANG are associated with neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Fronto-temporal dementia (FTD). ANG is a secreted protein which is taken up by cells and translocated to the nucleus. However, the import pathway/s through which ANG is taken up is/are still largely unclear. We have characterised the uptake of ANG in neuronal, astrocytic and microglial cell lines as well as primary neurons and astrocytes using pharmacological agents as well as dominant negative dynamin and Rab5 to perturb uptake and intracellular trafficking. We find that uptake of ANG is largely clathrin/dynamin independent and microtubule depolymerisation has a marginal effect. Perturbation of membrane ruffling and macropinocytosis significantly inhibited ANG uptake suggesting an uptake mechanism similar to RNase A. Our findings shed light on why mutations which do not overtly affect RNase activity but cause impaired localization are associated with neurodegenerative disease.

LanguageEnglish
Pagese0193302
JournalPLoS ONE
Volume13
Issue number2
DOIs
StatusPublished - 27 Feb 2018

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Dynamins
neurotrophins
Angiogenesis Inducing Agents
Nerve Growth Factors
uptake mechanisms
neurodegenerative diseases
Neurodegenerative diseases
mutation
Ribonucleases
clathrin
Neurodegenerative Diseases
dementia
depolymerization
astrocytes
imports
microtubules
stem cells
homeostasis
Pancreatic Ribonuclease
Clathrin

Keywords

  • Journal Article

Cite this

The cellular uptake of angiogenin, an angiogenic and neurotrophic factor is through multiple pathways and largely dynamin independent. / Ferguson, Ross; Subramanian, Vasanta.

In: PLoS ONE, Vol. 13, No. 2, 27.02.2018, p. e0193302.

Research output: Contribution to journalArticle

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