Protein Modification by Amino Acid Addition Is Increased in Crushed Sciatic But Not Optic Nerves

Shyne-Athwal, S.; Riccio, RV; Chakraborty, Goutam; Ingoglia, Nicholas A.

doi:10.1126/science.3080804

Cited by 44 publications

(22 citation statements)

References 19 publications

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“…; Shyne‐Athwal et al . ; Chakraborty and Ingoglia ). Such differential effects of Arg incorporation into proteins following damage to nerves of the peripheral nervous system (PNS) versus central nervous system (CNS) suggest that triggering of post‐translational protein arginylation may be related to the greater plasticity often observed for PNS nerves in response to various types of injury.…”

Section: Nerve Regeneration and Protein Arginylationmentioning

confidence: 99%

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

Galiano

Goitea

Hallak

2016

Journal of Neurochemistry

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Post-translational arginylation of proteins is an important regulator of many physiological pathways in cells. This modification was originally noted in protein degradation during neurodegenerative processes, with an apparently different physiological relevance between central and peripheral nervous system. Subsequent studies have identified a steadily increasing number of proteins and proteolysis-derived polypeptides as arginyltransferase (ATE1) substrates, including b-amyloid, a-synuclein, and TDP43 proteolytic fragments. Arginylation is involved in signaling processes of proteins and polypeptides that are further ubiquitinated and degraded by the proteasome. In addition, it is also implicated in autophagy/ lysosomal degradation pathway. Recent studies using mutant mouse strains deficient in ATE1 indicate additional roles of this modification in neuronal physiology. As ATE1 is capable of modifying proteins either at the N-terminus or middle-chain acidic residues, determining which proteins function are modulated by arginylation represents a big challenge. Here, we review studies addressing various roles of ATE1 activity in nervous system function, and suggest future research directions that will clarify the role of post-translational protein arginylation in brain development and various neurological disorders.

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Section: Nerve Regeneration and Protein Arginylationmentioning

confidence: 99%

“…Low or absent ATE1 activity may be associated with the lack of regenerative capacity characteristic of mammalian CNS nerves (Shyne‐Athwal et al . ; Chakraborty and Ingoglia ). Regenerative responses in PNS nerves involve coordination of multiple separate processes (Gumy et al .…”

Section: Roles Of Ate1 In the Nervous System Beyond Protein Degradationmentioning

confidence: 99%

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

Galiano

Goitea

Hallak

2016

Journal of Neurochemistry

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“…et al (1992) and Shyne-Athwal et al (1986) found that in vitro arginylated proteins obtained from damaged sciatic nerves are recognized by an antibody to ubiquitin and that the arginylation reaction is activated during nervous system regeneration. However, arginylation is not always the signal for the binding of ubiquitin.…”

Section: Introductionmentioning

confidence: 98%

Posttranslational arginylation of soluble rat brain proteins after whole body hyperthermia

et al. 1999

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We have previously reported the posttranslational addition of [14C]-arginine in the N-terminus of several soluble rat brain proteins. One of these proteins was identified as the microtubule-associated protein, the stable tubule only polypeptide (STOP). However, despite the fact that the biological significance of arginylation is not completely understood, some evidence associates it with proteolysis via the ubiquitin pathway. Since this degradative via is exacerbated as a response to stress, we studied in vitro the posttranslational [14C]-arginylation of cytosolic brain proteins of rats subjected to hyperthermia in vivo. Immediately after subjecting the animals to hyperthermia, a minor reduction (16%) in the acceptor capacity of [14C]-arginine into proteins was observed in comparison with animals maintained at 28 degrees C. However, in the animals allowed to recover for 3 h, an increase (46%) in the arginylation was observed concomitantly with a significant accumulation of the heat shock protein (70 kDa; hsp 70) when compared to the control animals. These findings suggest that the posttranslational arginylation of proteins participate in the heat shock response. The STOP protein of the soluble brain fraction of control animals, which in Western blot appears as a doublet band (125 and 130 kDa, respectively), is seen, after the hyperthermic treatment, as a single band of 125 kDa. The amount of 125 kDa protein, as well as the in vitro incorporation of [14C]-arginine, increases after hyperthermia in comparison with control animals. Following hyperthermic treatment, we observed a decrease in the amount of in vivo [35S]-methionine-labeled brain proteins. We speculate that, as observed for STOP protein, the increase in the degradation of protein that occurs in hyperthermia, would produce an increase in the amount of arginine acceptor proteins.

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“…This system operates, in part, as a mechanism whereby damaged proteins can be removed from the cytoplasm of a cell. We have found increases in posttranslational arginylation of proteins within 2 h of crush injury to sciatic nerves (Shyne-Athwal et al, 1988) and have speculated that these modifications are targeting damaged proteins for ubiquitin-mediated degradation (Shyne-Athwal et al, 1986, 1988Chakraborty et al, 1990b;Luo et al, 1990). Results of recent experiments support this speculation.…”

Section: Discussionmentioning

confidence: 81%

Evidence that Axonal tRNAs Are Resistant to RNase and ATPase and Can Be Aminoacylated in the Absence of Exogenous ATP

Chakraborty

Nicola

Ingoglia

1992

Journal of Neurochemistry

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A high molecular weight (HMW) fraction of the 150,000 g supernatant of rat brain homogenates contains protein-tRNA complexes which are able to incorporate [3H]Arg and [3H]Lys into tRNA. The aminoacylation of tRNA(Arg) was found to be dependent on ATP and inhibited by RNase. Conversely, the aminoacylation of tRNA(Lys) did not require exogenous ATP and was resistant to RNase and ATPase. In HMW fractions of regenerating rat sciatic nerves, the charging of both tRNA(Arg) and tRNA(Lys) was resistant to RNase and ATPase and did not require exogenous ATP. Because sciatic nerves are rich in axoplasm and tRNAs are known to be present in axons, we tested the hypothesis that degradative enzyme-resistant, ATP-tRNA complexes were of axonal origin. In HMW fractions from rat liver (containing no axons), both tRNA(Arg) and tRNA(Lys) were sensitive to RNase and required exogenous ATP for charging. But, in similar fractions of axoplasm obtained from the giant axon of squid, both tRNAs were insensitive to RNase and ATPase and did not require exogenous ATP for charging. These results suggest that tRNAs in axons are present in protected HMW complexes and contain endogenous stores of ATP. The presence of ATP in the HMW complexes was demonstrated by the luciferase-luciferin assay for ATP. The nature of the protection of tRNAs from RNases was examined by dissociating proteins from HMW complexes by boiling, treating with proteinase K, or overhomogenizing the tissue. These procedures failed to render brain tRNA(Lys) susceptible to RNase. But phenol-extracted, ethanol-precipitated brain tRNA(Lys) was sensitive to RNase, suggesting that the protection of tRNA(Lys) may be by a protease- and heat-resistant polypeptide or by a nonproteinaceous mechanism.

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Protein Modification by Amino Acid Addition Is Increased in Crushed Sciatic But Not Optic Nerves

Cited by 44 publications

References 19 publications

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

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

Posttranslational arginylation of soluble rat brain proteins after whole body hyperthermia

Evidence that Axonal tRNAs Are Resistant to RNase and ATPase and Can Be Aminoacylated in the Absence of Exogenous ATP

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