Variants in ANG are associated with neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). Although its identity to RNAse A at the amino acid level is only 33%, the overall three dimensional structure is similar to RNAse A. ANG has a characteristic “CKXXNTF” signature motif, the catalytic triad, and six conserved cysteine residues and a signal peptide. The RNAse A superfamily comprises 8 canonical members, which includes the pancreatic ribonuclease (RNase 1 or A), eosinophil-derived neurotoxin (or RNase 2), eosinophil cationic protein (or RNase 3), RNase 4, angiogenin (ANG or RNase 5), RNase 6 (or k6), RNase 7, and RNase 8. Our findings shed light on why mutations which do not overtly affect RNase activity but cause impaired localization are associated with neurodegenerative disease.Īngiogenin (ANG, also known as RNase 5) is a member of RNase A superfamily with a weak ribonucleolytic activity. Perturbation of membrane ruffling and macropinocytosis significantly inhibited ANG uptake suggesting an uptake mechanism similar to RNase A. We find that uptake of ANG is largely clathrin/dynamin independent and microtubule depolymerisation has a marginal effect. 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. However, the import pathway/s through which ANG is taken up is/are still largely unclear. ANG is a secreted protein which is taken up by cells and translocated to the nucleus. Mutations in ANG are associated with neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Fronto-temporal dementia (FTD).
Recently it has also been shown to be important in stem cell homeostasis. Angiogenin (ANG), a member of the RNase superfamily (also known as RNase 5) has neurotrophic, neuroprotective and angiogenic activities.
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