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PMID: 15673657 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 25 ·No. 4 ·2005-01-26 ·Pages 778-91

Willis D, Li KW, Zheng JQ, Chang JH, Smit AB, Smit A, Kelly T, Merianda TT, Sylvester J, van Minnen J, Twiss JL

Abstract

Recent studies have begun to focus on the signals that regulate axonal protein synthesis and the functional significance of localized protein synthesis. However, identification of proteins that are synthesized in mammalian axons has been mainly based on predictions. Here, we used axons purified from cultures of injury-conditioned adult dorsal root ganglion (DRG) neurons and proteomics methodology to identify axonally synthesized proteins. Reverse transcription (RT)-PCR from axonal preparations was used to confirm that the mRNA for each identified protein extended into the DRG axons. Proteins and the encoding mRNAs for the cytoskeletal proteins beta-actin, peripherin, vimentin, gamma-tropomyosin 3, and cofilin 1 were present in the axonal preparations. In addition to the cytoskeletal elements, several heat shock proteins (HSP27, HSP60, HSP70, grp75, alphaB crystallin), resident endoplasmic reticulum (ER) proteins (calreticulin, grp78/BiP, ERp29), proteins associated with neurodegenerative diseases (ubiquitin C-terminal hydrolase L1, rat ortholog of human DJ-1/Park7, gamma-synuclein, superoxide dismutase 1), anti-oxidant proteins (peroxiredoxins 1 and 6), and metabolic proteins (e.g., phosphoglycerate kinase 1 (PGK 1), alpha enolase, aldolase C/Zebrin II) were included among the axonally synthesized proteins. Detection of the mRNAs encoding each of the axonally synthesized proteins identified by mass spectrometry in the axonal compartment indicates that the DRG axons have the potential to synthesize a complex population of proteins. Local treatment of the DRG axons with NGF or BDNF increased levels of cytoskeletal mRNAs into the axonal compartment by twofold to fivefold but had no effect on levels of the other axonal mRNAs studied. Neurotrophins selectively increased transport of beta-actin, peripherin, and vimentin mRNAs from the cell body into the axons rather than changing transcription or mRNA survival in the axonal compartment.

MeSH Terms
Animals Axons/metabolism Brain-Derived Neurotrophic Factor/physiology Cells, Cultured Cytoskeletal Proteins/biosynthesis,genetics Endoplasmic Reticulum/metabolism Endoplasmic Reticulum Chaperone BiP Ganglia, Spinal/cytology,metabolism Heat-Shock Proteins/biosynthesis,genetics Nerve Growth Factor/physiology Nerve Regeneration/physiology Nerve Tissue Proteins/biosynthesis,genetics Neurodegenerative Diseases/metabolism Neurons, Afferent/metabolism Protein Biosynthesis RNA Transport RNA, Messenger/metabolism Rats Rats, Sprague-Dawley Sciatic Nerve/injuries
Chemicals
Brain-Derived Neurotrophic Factor Cytoskeletal Proteins Endoplasmic Reticulum Chaperone BiP HSPA5 protein, human Heat-Shock Proteins Nerve Tissue Proteins RNA, Messenger Nerve Growth Factor
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Willis Dianna
Nemours Biomedical Research, Alfred I. DuPont Hospital for Children, Wilmington, Delaware 19803, USA.
Li Ka Wan
Zheng Jun-Qi
Chang Jay H
Smit August B
Smit August
Kelly Theresa
Merianda Tanuja T
Sylvester James
van Minnen Jan
Twiss Jeffery L
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4235-04.2005
Published
2005-01-26
Pages
778-91
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6725618
Subset
IM
Grants
NCRR NIH HHS · P20 RR020173 · United States
NINDS NIH HHS · R01 NS041596 · United States
NINDS NIH HHS · NS041596 · United States
NCRR NIH HHS · RR020173 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1523/JNEUROSCI.4235-04.2005 PMC Full Text View journal details
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