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Kir4.1-Dependent Astrocyte-Fast Motor Neuron Interactions Are Required for Peak Strength.

Neuron | 2018

Diversified neurons are essential for sensorimotor function, but whether astrocytes become specialized to optimize circuit performance remains unclear. Large fast α-motor neurons (FαMNs) of spinal cord innervate fast-twitch muscles that generate peak strength. We report that ventral horn astrocytes express the inward-rectifying K+ channel Kir4.1 (a.k.a. Kcnj10) around MNs in a VGLUT1-dependent manner. Loss of astrocyte-encoded Kir4.1 selectively altered FαMN size and function and led to reduced peak strength. Overexpression of Kir4.1 in astrocytes was sufficient to increase MN size through activation of the PI3K/mTOR/pS6 pathway. Kir4.1 was downregulated cell autonomously in astrocytes derived from amyotrophic lateral sclerosis (ALS) patients with SOD1 mutation. However, astrocyte Kir4.1 was dispensable for FαMN survival even in the mutant SOD1 background. These findings show that astrocyte Kir4.1 is essential for maintenance of peak strength and suggest that Kir4.1 downregulation might uncouple symptoms of muscle weakness from MN cell death in diseases like ALS.

Pubmed ID: 29606582 RIS Download

Research resources used in this publication

Antibodies used in this publication

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS040511
  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_12009
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007618
  • Agency: Medical Research Council, United Kingdom
    Id: MR/P008658/1
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH106490
  • Agency: NIMH NIH HHS, United States
    Id: K08 MH104417
  • Agency: Wellcome Trust, United Kingdom
  • Agency: NEI NIH HHS, United States
    Id: P30 EY002162

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This is a list of tools and resources that we have found mentioned in this publication.


BioLegend (tool)

RRID:SCR_001134

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Addgene (tool)

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Jackson Laboratory (tool)

RRID:SCR_004633

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Ensembl (tool)

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Collection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.

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affy (tool)

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NTac:SD-Tg(SOD1G93A)L26H (tool)

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Anti-β-Actin Antibody (antibody)

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ALDH1L1 antibody - Astrocyte Marker (antibody)

RRID:AB_10712968

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Anti-Matrix Metalloproteinase-9 antibody produced in goat (antibody)

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Anti-Kir4.1 (KCNJ10) (extracellular) Antibody (antibody)

RRID:AB_2341043

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Anti-Kir4.1 (KCNJ10) Antibody (antibody)

RRID:AB_2040120

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RRID:AB_476744

This monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH

View all literature mentions

ALDH1L1 antibody - Astrocyte Marker (antibody)

RRID:AB_10712968

This polyclonal targets ALDH1L1 antibody - Astrocyte Marker

View all literature mentions

Anti-VGluT2 Antibody (antibody)

RRID:AB_2665454

This polyclonal targets VGluT2

View all literature mentions

Anti-NeuN (antibody)

RRID:AB_2298772

This monoclonal targets NeuN

View all literature mentions

Monoclonal Anti-Myosin (Skeletal, Slow) antibody produced in mouse (antibody)

RRID:AB_477248

This monoclonal targets Myosin (Skeletal Slow) antibody produced in mouse

View all literature mentions

Anti-Matrix Metalloproteinase-9 antibody produced in goat (antibody)

RRID:AB_1079397

This unknown targets Mouse Matrix Metalloproteinase-9

View all literature mentions

Anti-Laminin antibody produced in rabbit (antibody)

RRID:AB_477163

This polyclonal targets Laminin antibody produced in rabbit

View all literature mentions

Anti-Kir4.1 (KCNJ10) (extracellular) Antibody (antibody)

RRID:AB_2341043

This unknown targets Kir4.1 (KCNJ10) Channel

View all literature mentions

Anti-Kir4.1 (KCNJ10) Antibody (antibody)

RRID:AB_2040120

This unknown targets Kir4.1 (KCNJ10) Channel

View all literature mentions

Anti-Green Fluorescent Protein Antibody (antibody)

RRID:AB_10000240

This polyclonal targets Green Fluorescent Protein (GFP)

View all literature mentions

Anti-Choline Acetyltransferase Antibody (antibody)

RRID:AB_2079751

This polyclonal targets Choline Acetyltransferase

View all literature mentions