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Neuron. 2016 Nov 23;92(4):857-872. doi: 10.1016/j.neuron.2016.10.003. Epub 2016 Nov 3.

Activity-Dependent Regulation of Distinct Transport and Cytoskeletal Remodeling Functions of the Dendritic Kinesin KIF21B.

Author information

1
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
2
Department of Molecular Neurogenetics, ZMNH, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
3
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA. Electronic address: holzbaur@mail.med.upenn.edu.

Abstract

The dendritic arbor is subject to continual activity-dependent remodeling, requiring a balance between directed cargo trafficking and dynamic restructuring of the underlying microtubule tracks. How cytoskeletal components are able to dynamically regulate these processes to maintain this balance remains largely unknown. By combining single-molecule assays and live imaging in rat hippocampal neurons, we have identified the kinesin-4 KIF21B as a molecular regulator of activity-dependent trafficking and microtubule dynamicity in dendrites. We find that KIF21B contributes to the retrograde trafficking of brain-derived neurotrophic factor (BDNF)-TrkB complexes and also regulates microtubule dynamics through a separable, non-motor microtubule-binding domain. Neuronal activity enhances the motility of KIF21B at the expense of its role in cytoskeletal remodeling, the first example of a kinesin whose function is directly tuned to neuronal activity state. These studies suggest a model in which KIF21B navigates the complex cytoskeletal environment of dendrites by compartmentalizing functions in an activity-dependent manner.

KEYWORDS:

BDNF; KIF21B; TrkB; dendrite; kinesin; microtubules

PMID:
27817978
PMCID:
PMC5283298
DOI:
10.1016/j.neuron.2016.10.003
[Indexed for MEDLINE]
Free PMC Article

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