Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites
0301 basic medicine
calmodulin
QH301-705.5
Dendritic Spines
General Biochemistry,Genetics and Molecular Biology
Kinesins
Nerve Tissue Proteins
scaffold
TANC2
Article
03 medical and health sciences
Calmodulin
synapse
Animals
Humans
Biology (General)
Rats, Wistar
KIF1A
Adaptor Proteins, Signal Transducing
0303 health sciences
calcium
liprin-α
Secretory Vesicles
Intracellular Signaling Peptides and Proteins
dendritic spines
neuron
3. Good health
HEK293 Cells
transport
Mutation
Synapses
Calcium
Protein Binding
DOI:
10.1016/j.celrep.2018.06.071
Publication Date:
2018-07-17T14:45:48Z
AUTHORS (9)
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.
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