CLIP-170 and IQGAP1 cooperatively regulate dendrite morphology

Dendritic arbors are compartments of neurons dedicated to receiving synaptic inputs. Their shape is an outcome of both the intrinsic genetic program and environmental signals. The microtubules and actin cytoskeleton are both crucial for proper dendritic morphology, but how they interact is unclear....

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Bibliographic Details
Published in:The Journal of neuroscience 2011-03, Vol.31 (12), p.4555-4568
Main Authors: Swiech, Lukasz, Blazejczyk, Magdalena, Urbanska, Malgorzata, Pietruszka, Patrycja, Dortland, Bjorn R, Malik, Anna R, Wulf, Phebe S, Hoogenraad, Casper C, Jaworski, Jacek
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Biotinylation
Cells, Cultured
Cytoskeleton - physiology
Cytoskeleton - ultrastructure
Dendrites - physiology
Dendrites - ultrastructure
DNA - genetics
Fluorescent Antibody Technique
Green Fluorescent Proteins
Hippocampus - cytology
Hippocampus - physiology
Image Processing, Computer-Assisted
Indicators and Reagents
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - physiology
Microtubules - physiology
Microtubules - ultrastructure
Neoplasm Proteins - genetics
Neoplasm Proteins - physiology
Phosphatidylinositol 3-Kinases - metabolism
Phosphatidylinositol 3-Kinases - physiology
Phosphorylation
ras GTPase-Activating Proteins - genetics
ras GTPase-Activating Proteins - physiology
Rats
TOR Serine-Threonine Kinases - metabolism
Transfection
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Summary:Dendritic arbors are compartments of neurons dedicated to receiving synaptic inputs. Their shape is an outcome of both the intrinsic genetic program and environmental signals. The microtubules and actin cytoskeleton are both crucial for proper dendritic morphology, but how they interact is unclear. The present study demonstrates that microtubule plus-end tracking protein CLIP-170 and actin-binding protein IQGAP1 regulate dendrite morphology of rat neurons by coordinating the interaction between microtubules and the actin cytoskeleton. Moreover, we show that mTOR kinase interacts with CLIP-170 and is needed for efficient formation of a protein complex containing CLIP-170 and IQGAP1. Dynamic microtubules, CLIP-170, and IQGAP1 are required for proper dendritic arbor morphology and PI3K-mTOR-induced increase in dendritic arbor complexity. Moreover, CLIP-170 and IQGAP1 knockdown modulates dendritic arbor growth via regulation of the actin cytoskeleton. We postulate that mTOR controls dendritic arbor morphology by enhancing cross talk between dynamic microtubules and actin through CLIP-170 and IQGAP1.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.6582-10.2011