Document Detail


Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern.
MedLine Citation:
PMID:  24291744     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transient receptor potential, melastatin-like 7 (Trpm7) is a combined ion channel and kinase implicated in the differentiation or function of many cell types. Early lethality in mice and frogs depleted of the corresponding gene impedes investigation of the functions of this protein particularly during later stages of development. By contrast, zebrafish trpm7 mutant larvae undergo early morphogenesis normally and thus do not have this limitation. The mutant larvae are characterized by multiple defects including melanocyte cell death, transient paralysis, and an ion imbalance that leads to the development of kidney stones. Here we report a requirement for Trpm7 in differentiation or function of dopaminergic neurons in vivo. First, trpm7 mutant larvae are hypomotile and fail to make a dopamine-dependent developmental transition in swim-bout length. Both of these deficits are partially rescued by the application of levodopa or dopamine. Second, histological analysis reveals that in trpm7 mutants a significant fraction of dopaminergic neurons lack expression of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Third, trpm7 mutants are unusually sensitive to the neurotoxin 1-methyl-4-phenylpyridinium, an oxidative stressor, and their motility is partially rescued by application of the iron chelator deferoxamine, an anti-oxidant. Finally, in SH-SY5Y cells, which model aspects of human dopaminergic neurons, forced expression of a channel-dead variant of TRPM7 causes cell death. In summary, a forward genetic screen in zebrafish has revealed that both melanocytes and dopaminergic neurons depend on the ion channel Trpm7. The mechanistic underpinning of this dependence requires further investigation.
Authors:
Amanda R Decker; Matthew S McNeill; Aaron M Lambert; Jeffrey D Overton; Yu-Chia Chen; Ramón A Lorca; Nicolas A Johnson; Susan E Brockerhoff; Durga P Mohapatra; Heather MacArthur; Pertti Panula; Mark A Masino; Loren W Runnels; Robert A Cornell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-11-27
Journal Detail:
Title:  Developmental biology     Volume:  386     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-01-28     Completed Date:  2014-03-26     Revised Date:  2014-11-16    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  428-39     Citation Subset:  IM    
Copyright Information:
© 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenylpyridinium / toxicity
Analysis of Variance
Animals
Cell Differentiation / physiology*
Cell Line
DNA Primers / genetics
Deferoxamine / pharmacology
Dopaminergic Neurons / cytology*
Electroretinography
Larva / growth & development
Melanocytes / metabolism
Motor Activity / drug effects,  genetics*,  physiology
Mutation / genetics
Patch-Clamp Techniques
Protein-Serine-Threonine Kinases / genetics*
Reverse Transcriptase Polymerase Chain Reaction
TRPM Cation Channels / genetics*
Tyrosine 3-Monooxygenase / metabolism
Zebrafish / genetics,  growth & development*
Zebrafish Proteins / genetics*
Grant Support
ID/Acronym/Agency:
GM067841/GM/NIGMS NIH HHS; NS065054/NS/NINDS NIH HHS; NS069898/NS/NINDS NIH HHS; P30 ES05605/ES/NIEHS NIH HHS; P30EY001730/EY/NEI NIH HHS; R01 GM067841/GM/NIGMS NIH HHS; R01 GM080753/GM/NIGMS NIH HHS; R01EY015165/EY/NEI NIH HHS; R01EY018814/EY/NEI NIH HHS; R01GM080753/GM/NIGMS NIH HHS; T32 GM008471/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/TRPM Cation Channels; 0/Zebrafish Proteins; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Trpm7 protein, zebrafish; J06Y7MXW4D/Deferoxamine; R865A5OY8J/1-Methyl-4-phenylpyridinium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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