Post-translational protein arginylation in the normal nervous system and in neurodegeneration

MARTA E. HALLAK; VICTOR E. GOITEA; MAURICIO R. GALIANO

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016

0022-3042

Post-translational arginylation of proteins is an importantregulator of many physiological pathways in cells. Thismodication was originally noted in protein degradation duringneurodegenerative processes, with an apparently differentphysiological relevance between central and peripheral nervoussystem. Subsequent studies have identied a steadilyincreasing number of proteins and proteolysis-derivedpolypeptides as arginyltransferase (ATE1) substrates, includingb-amyloid, a-synuclein, and TDP43 proteolytic fragments.Arginylation is involved in signaling processes of proteins andpolypeptides that are further ubiquitinated and degraded bythe proteasome. In addition, it is also implicated in autophagy/lysosomal degradation pathway. Recent studies using mutantmouse strains decient in ATE1 indicate additional roles of thismodication in neuronal physiology. As ATE1 is capable ofmodifying proteins either at the N-terminus or middle-chainacidic residues, determining which proteins function aremodulated by arginylation represents a big challenge. Here,we review studies addressing various roles of ATE1 activity innervous system function, and suggest future research directionsthat will clarify the role of post-translational proteinarginylation in brain development and various neurologicaldisorders.