Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites

Cell Rep. 2018 Jul 17;24(3):685-700. doi: 10.1016/j.celrep.2018.06.071.


Tight regulation of neuronal transport allows for cargo binding and release at specific cellular locations. The mechanisms by which motor proteins are loaded on vesicles and how cargoes are captured at appropriate sites remain unclear. To better understand how KIF1A-driven dense core vesicle (DCV) transport is regulated, we identified the KIF1A interactome and focused on three binding partners, the calcium binding protein calmodulin (CaM) and two synaptic scaffolding proteins: liprin-α and TANC2. We showed that calcium, acting via CaM, enhances KIF1A binding to DCVs and increases vesicle motility. In contrast, liprin-α and TANC2 are not part of the KIF1A-cargo complex but capture DCVs at dendritic spines. Furthermore, we found that specific TANC2 mutations-reported in patients with different neuropsychiatric disorders-abolish the interaction with KIF1A. We propose a model in which Ca2+/CaM regulates cargo binding and liprin-α and TANC2 recruit KIF1A-transported vesicles.

Keywords: KIF1A; TANC2; calcium; calmodulin; dendritic spines; liprin-α; neuron; scaffold; synapse; transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Calcium / metabolism*
  • Calmodulin / metabolism*
  • Dendritic Spines / metabolism
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kinesins / metabolism*
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • Rats, Wistar
  • Secretory Vesicles / metabolism*
  • Synapses / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Calmodulin
  • Intracellular Signaling Peptides and Proteins
  • Kif1a protein, rat
  • Nerve Tissue Proteins
  • Ppfia1 protein, rat
  • Tanc2 protein, rat
  • Kinesins
  • Calcium