The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory.
The kinesin KIF21B is implicated in several human neurological disorders, including delayed cognitive development, yet it remains unclear how KIF21B dysfunction may contribute to pathology. One limitation is that relatively little is known about KIF21B-mediated physiological functions. Here, we generated Kif21b knockout mice and used cellular assays to investigate the relevance of KIF21B in neuronal and in vivo function. We show that KIF21B is a processive motor protein and identify an additional role for KIF21B in regulating microtubule dynamics. In neurons lacking KIF21B, microtubules grow more slowly and persistently, leading to tighter packing in dendrites. KIF21B-deficient neurons exhibit decreased dendritic arbor complexity and reduced spine density, which correlate with deficits in synaptic transmission. Consistent with these observations, Kif21b-null mice exhibit behavioral changes involving learning and memory deficits. Our study provides insight into the cellular function of KIF21B and the basis for cognitive decline resulting from KIF21B dysregulation.
Department of Molecular Neurogenetics, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Mary
M
Muhia
Department of Molecular Neurogenetics, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Edda
E
Thies
Department of Molecular Neurogenetics, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Dorthe
D
Labonté
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA.
Amy E
AE
Ghiretti
Department of Molecular Neurogenetics, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Kira V
KV
Gromova
Department of Molecular and Cellular Cognition, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Francesca
F
Xompero
Department of Molecular Neurogenetics, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Corinna
C
Lappe-Siefke
Transgenic Animal Unit, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Irm
I
Hermans-Borgmeyer
Department of Molecular and Cellular Cognition, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Dietmar
D
Kuhl
Morphology Unit, Center for Molecular Neurobiology ZMNH, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Michaela
M
Schweizer
Department of Molecular and Cellular Cognition, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Ora
O
Ohana
Department of Molecular Neurogenetics, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
Jürgen R
JR
Schwarz
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA.
Erika L F
ELF
Holzbaur
Department of Molecular Neurogenetics, University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany. Electronic address: matthias.kneussel@zmnh.uni-hamburg.de.
Matthias
M
Kneussel
D000818:Animals; D048430:Cell Shape; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D018390:Gene Targeting; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000172:deficiency / Q000378:metabolism*; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D015203:Reproducibility of Results; D013569:Synapses / Q000378:metabolism*
C119024:Kif21b protein, mouse; D016547:Kinesins
KIF21B; LTP; dendrite; kinesin; learning and memory; microtubule dynamics; neuron; spine; synapse