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

• Published in: Neuron (Cambridge, Mass.) Vol. 92; no. 4; pp. 857 - 872
• Main Authors: Ghiretti, Amy E., Thies, Edda, Tokito, Mariko K., Lin, Tianming, Ostap, E. Michael, Kneussel, Matthias, Holzbaur, Erika L.F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.11.2016; Elsevier Limited
• Subjects: Animals; Baas; BDNF; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cytoskeleton; Cytoskeleton - metabolism; dendrite; Dendrites; Dendrites - metabolism; Experiments; Gene Knockout Techniques; Hippocampus; Hippocampus - cytology; KIF21B; Kinesin; Kinesin - genetics; Kinesin - metabolism; Localization; microtubules; Microtubules - metabolism; Motility; Neuroimaging; Neurons; Neurons - metabolism; Protein Transport - genetics; Protein-Tyrosine Kinases - metabolism; Proteins; Rats; Receptor, trkB; TrkB; TrkB receptors; Fiji; dendrite; TrkB; KIF21B; microtubules; BDNF; kinesin
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2016.10.003

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. •KIF21B dually regulates trafficking and microtubule dynamics in dendrites•KIF21B is involved in proper retrograde trafficking of BDNF-bound TrkB receptors•Regulation of microtubule dynamicity by KIF21B is independent of motor activity•Activity downregulates KIF21B microtubule remodeling activity, but not motor function Ghiretti et al. demonstrate that the dendritic kinesin KIF21B independently regulates transport and microtubule dynamicity through discrete microtubule binding sites. Uniquely, regulation of dynamicity is independent of motor activity, and neuronal activity differentially regulates the dual functions of this kinesin.