4.8 Article

Molecular motor protein KIF5C mediates structural plasticity and long-term memory by constraining local translation

Journal

CELL REPORTS
Volume 36, Issue 2, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2021.109369

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Funding

  1. NIH [5R01MH094607-05, 5R21MH108929-02]
  2. NSF [1453799]
  3. Training Grant in Alzheimer's Drug Discovery from the Lottie French Lewis Fund of the Community Foundation
  4. Division Of Integrative Organismal Systems
  5. Direct For Biological Sciences [1453799] Funding Source: National Science Foundation

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The study reveals the roles of KIF5C and KIF3A in synaptic structural plasticity and memory storage. KIF5C is a key component of local translation, associated with numerous RNAs, and its loss of function affects spatial and contextual fear memory.
Synaptic structural plasticity, key to long-term memory storage, requires translation of localized RNAs delivered by long-distance transport from the neuronal cell body. Mechanisms and regulation of this system remain elusive. Here, we explore the roles of KIF5C and KIF3A, two members of kinesin superfamily of molecular motors (Kifs), and find that loss of function of either kinesin decreases dendritic arborization and spine density whereas gain of function of KIF5C enhances it. KIF5C function is a rate-determining component of local translation and is associated with similar to 650 RNAs, including EIF3G, a regulator of translation initiation, and plasticity-associated RNAs. Loss of function of KIF5C in dorsal hippocampal CA1 neurons constrains both spatial and contextual fear memory, whereas gain of function specifically enhances spatial memory and extinction of contextual fear. KIF5C-mediated long-distance transport of local translation substrates proves a key mechanism underlying structural plasticity and memory.

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