TY - JOUR
T1 - Regulation of KIF1A-Driven Dense Core Vesicle Transport
T2 - Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites
AU - Stucchi, Riccardo
AU - Plucińska, Gabriela
AU - Hummel, Jessica J.A.
AU - Zahavi, Eitan E.
AU - Guerra San Juan, Irune
AU - Klykov, Oleg
AU - Scheltema, Richard A.
AU - Altelaar, A. F.Maarten
AU - Hoogenraad, Casper C.
PY - 2018/7/17
Y1 - 2018/7/17
N2 - 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.
AB - 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.
KW - calcium
KW - calmodulin
KW - dendritic spines
KW - KIF1A
KW - liprin-α
KW - neuron
KW - scaffold
KW - synapse
KW - TANC2
KW - transport
UR - http://www.scopus.com/inward/record.url?scp=85049834039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049834039&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.06.071
DO - 10.1016/j.celrep.2018.06.071
M3 - Article
C2 - 30021165
AN - SCOPUS:85049834039
SN - 2211-1247
VL - 24
SP - 685
EP - 700
JO - Cell Reports
JF - Cell Reports
IS - 3
ER -