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

Riccardo Stucchi, Gabriela Plucińska, Jessica J.A. Hummel, Eitan E. Zahavi, Irune Guerra San Juan, Oleg Klykov, Richard A. Scheltema, A. F.Maarten Altelaar, Casper C. Hoogenraad*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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. Stucchi et al. show that KIF1A-dependent transport is regulated by CaM, liprin-α and TANC2. KIF1A binding to DCVs is controlled by a Ca2+/CaM molecular mechanism, and KIF1A-driven DCVs are recruited in dendritic spines by the PSD scaffolds liprin-α and TANC2.

Original languageEnglish
Pages (from-to)685-700
Number of pages16
JournalCell Reports
Volume24
Issue number3
DOIs
Publication statusPublished - 17 Jul 2018
Externally publishedYes

Keywords

  • calcium
  • calmodulin
  • dendritic spines
  • KIF1A
  • liprin-α
  • neuron
  • scaffold
  • synapse
  • TANC2
  • transport

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