The kinesin Kif21b binds myosin Va and mediates changes in actin dynamics underlying homeostatic synaptic downscaling

Cell Rep. 2023 Jul 25;42(7):112743. doi: 10.1016/j.celrep.2023.112743. Epub 2023 Jul 6.


Homeostatic synaptic plasticity adjusts the strength of synapses to restrain neuronal activity within a physiological range. Postsynaptic guanylate kinase-associated protein (GKAP) controls the bidirectional synaptic scaling of AMPA receptors (AMPARs); however, mechanisms by which chronic activity triggers cytoskeletal remodeling to downscale synaptic transmission are barely understood. Here, we report that the microtubule-dependent kinesin motor Kif21b binds GKAP and likewise is located in dendritic spines in a myosin Va- and neuronal-activity-dependent manner. Kif21b depletion unexpectedly alters actin dynamics in spines, and adaptation of actin turnover following chronic activity is lost in Kif21b-knockout neurons. Consistent with a role of the kinesin in regulating actin dynamics, Kif21b overexpression promotes actin polymerization. Moreover, Kif21b controls GKAP removal from spines and the decrease of GluA2-containing AMPARs from the neuronal surface, thereby inducing homeostatic synaptic downscaling. Our data highlight a critical role of Kif21b at the synaptic actin cytoskeleton underlying homeostatic scaling of neuronal firing.

Keywords: AMPA receptor; CP: Neuroscience; GKAP; Kif21b; actin; dendritic spine; homeostatic synaptic plasticity; kinesin; myosin Va; neuron; synaptic downscaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Actins* / metabolism
  • Dendritic Spines / metabolism
  • Kinesins* / metabolism
  • Myosins / metabolism
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Synapses / metabolism


  • Actins
  • Kinesins
  • Myosins