Activity-Dependent Regulation of Distinct Transport and Cytoskeletal Remodeling Functions of the Dendritic Kinesin KIF21B.
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.
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Amy E
AE
Ghiretti
Department of Molecular Neurogenetics, ZMNH, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Edda
E
Thies
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Mariko K
MK
Tokito
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Tianming
T
Lin
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
E Michael
EM
Ostap
Department of Molecular Neurogenetics, ZMNH, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Matthias
M
Kneussel
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA. Electronic address: holzbaur@mail.med.upenn.edu.
Erika L F
ELF
Holzbaur
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006624:Hippocampus / Q000166:cytology; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D020813:Receptor, trkB
D019208:Brain-Derived Neurotrophic Factor; C000621230:Ntrk2 protein, rat; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000621381:Kif21b protein, rat; D016547:Kinesins
BDNF; KIF21B; TrkB; dendrite; kinesin; microtubules