Abstract
Neurons from the adult central nervous system (CNS) demonstrate limited mRNA transport and localized protein synthesis versus developing neurons, correlating with lower regenerative capacity. We found that deimination (posttranslational conversion of protein-bound arginine into citrulline) undergoes upregulation during early neuronal development while declining to a low basal level in adults. This modification is associated with neuronal arborization from amphibians to mammals. The mRNA-binding proteins (ANP32a, REF), deiminated in neurons, have been implicated in local protein synthesis. Overexpression of the deiminating cytosolic enzyme peptidyl arginine deiminase 2 in nervous systems results in increased neuronal transport and neurite outgrowth. We further demonstrate that enriching deiminated proteins rescues transport deficiencies both in primary neurons and mouse optic nerve even in the presence of pharmacological transport blockers. We conclude that deimination promotes neuronal outgrowth via enhanced transport and local protein synthesis and represents a new avenue for neuronal regeneration in the adult CNS.
| Original language | English (US) |
|---|---|
| Journal | Molecular Neurobiology |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- Deimination
- Development
- PAD2
- Regeneration
ASJC Scopus subject areas
- Neuroscience (miscellaneous)
- Neurology
- Cellular and Molecular Neuroscience
Cite this
The Role of Deimination in Regenerative Reprogramming of Neurons. / Ding, Di; Enriquez-Algeciras, Mabel; Valdivia, Anddre Osmar; Torres, Juan; Pole, Cameron; Thompson, John W.; Chou, Tsung han; Perez-Pinzon, Miguel; Porciatti, Vittorio; Udin, Susan; Nestler, Eric; Bhattacharya, Sanjoy K.
In: Molecular Neurobiology, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Role of Deimination in Regenerative Reprogramming of Neurons
AU - Ding, Di
AU - Enriquez-Algeciras, Mabel
AU - Valdivia, Anddre Osmar
AU - Torres, Juan
AU - Pole, Cameron
AU - Thompson, John W.
AU - Chou, Tsung han
AU - Perez-Pinzon, Miguel
AU - Porciatti, Vittorio
AU - Udin, Susan
AU - Nestler, Eric
AU - Bhattacharya, Sanjoy K
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Neurons from the adult central nervous system (CNS) demonstrate limited mRNA transport and localized protein synthesis versus developing neurons, correlating with lower regenerative capacity. We found that deimination (posttranslational conversion of protein-bound arginine into citrulline) undergoes upregulation during early neuronal development while declining to a low basal level in adults. This modification is associated with neuronal arborization from amphibians to mammals. The mRNA-binding proteins (ANP32a, REF), deiminated in neurons, have been implicated in local protein synthesis. Overexpression of the deiminating cytosolic enzyme peptidyl arginine deiminase 2 in nervous systems results in increased neuronal transport and neurite outgrowth. We further demonstrate that enriching deiminated proteins rescues transport deficiencies both in primary neurons and mouse optic nerve even in the presence of pharmacological transport blockers. We conclude that deimination promotes neuronal outgrowth via enhanced transport and local protein synthesis and represents a new avenue for neuronal regeneration in the adult CNS.
AB - Neurons from the adult central nervous system (CNS) demonstrate limited mRNA transport and localized protein synthesis versus developing neurons, correlating with lower regenerative capacity. We found that deimination (posttranslational conversion of protein-bound arginine into citrulline) undergoes upregulation during early neuronal development while declining to a low basal level in adults. This modification is associated with neuronal arborization from amphibians to mammals. The mRNA-binding proteins (ANP32a, REF), deiminated in neurons, have been implicated in local protein synthesis. Overexpression of the deiminating cytosolic enzyme peptidyl arginine deiminase 2 in nervous systems results in increased neuronal transport and neurite outgrowth. We further demonstrate that enriching deiminated proteins rescues transport deficiencies both in primary neurons and mouse optic nerve even in the presence of pharmacological transport blockers. We conclude that deimination promotes neuronal outgrowth via enhanced transport and local protein synthesis and represents a new avenue for neuronal regeneration in the adult CNS.
KW - Deimination
KW - Development
KW - PAD2
KW - Regeneration
UR - http://www.scopus.com/inward/record.url?scp=85050809893&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050809893&partnerID=8YFLogxK
U2 - 10.1007/s12035-018-1262-y
DO - 10.1007/s12035-018-1262-y
M3 - Article
C2 - 30051351
AN - SCOPUS:85050809893
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
ER -