TRIM3 Regulates the Motility of the Kinesin Motor Protein KIF21B

Abstract

Kinesin superfamily proteins (KIFs) are molecular motors that transport cellular cargo along the microtubule cytoskeleton. KIF21B is a neuronal kinesin that is highly enriched in dendrites. The regulation and specificity of microtubule transport involves the binding of motors to individual cargo adapters and accessory proteins. Moreover, posttranslational modifications of either the motor protein, their cargos or tubulin regulate motility, cargo recognition and the binding or unloading of cargos. Here we show that the ubiquitin E3 ligase TRIM3, also known as BERP, interacts with KIF21B via its RBCC domain. TRIM3 is found at intracellular and Golgi-derived vesicles and co-localizes with the KIF21B motor in neurons. Trim3 gene deletion in mice and TRIM3 overexpression in cultured neurons both suggested that the E3-ligase function of TRIM3 is not involved in KIF21B degradation, however TRIM3 depletion reduces the motility of the motor. Together, our data suggest that TRIM3 is a regulator in the modulation of KIF21B motor function.

Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels

“…Together, these findings establish that TRIM3 is a ubiquitin ligase that is localized to dendritic compartments, including postsynaptic sites, as previously shown by Hung et al (2010). Behavioral analysis of 3-mo-old Trim3 −/− mice (Labonté et al, 2013) did not reveal important alterations in anxiety and locomotor behavior using open field, dark-light box, and elevated plus maze tests (Table 1). However, in a hippocampus-dependent contextual fear memory task, Trim3 −/− mice showed enhanced memory acquisition.…”

“…The generation of Trim3 −/− mice was described previously (Labonté et al, 2013). Actg1 lox/lox mice (Perrin et al, 2010; gift of J. Ervasti, University of Minnesota, Minneapolis, MN) were crossed with Camk2a-Cre mice (Mantamadiotis et al, 2002) to generate Actg1 cKO mice.…”

Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers, FGF22 and FGF7

“…The scrambled sequence for control shRNA was: 59-GCGCGCTTTGTAGGATTCG-39. The knockdown efficiency was verified by a massive reduction in the amount of KIF21B as shown by immunostaining and western blotting (Labonté et al, 2013).…”

“…KIF5 is involved in the transportation of the GABA A receptor, glycine receptor and AMPA receptor (Maas et al, 2006;Nakajima et al, 2012;Setou et al, 2002;Smith et al, 2006); KIF3A localizes to excitatory postsynaptic terminals and is involved in AMPA receptor transportation (Lin et al, 2012); KIF17 is a dendritic motor involved in NMDA receptor transportation (Jo et al, 1999;Setou et al, 2000); and KIF21B is highly enriched in dendrites (Marszalek et al, 1999). To examine whether these KIFs are involved in FGF22 transport, we generated GFP-tagged dominant negative (DN) mutants for KIF5, KIF3A and KIF17, and short hairpin RNA (shRNA) for KIF21B (Labonté et al, 2013). DN-KIFs, which are also known as 'headless' mutants, contain the cargo-binding domain and no motor domain (Chu et al, 2006;Falley et al, 2009;Sathish et al, 2009;Uchida et al, 2009), and are mainly restricted to the cell body.…”

The kinesin KIF21B participates in the cell surface delivery of γ2 subunit-containing GABAA receptors

“…In neurons, this motor is enriched in dendrites and growth cones at neurite tips (Labonte et al, 2013;Marszalek et al, 1999). The motility of KIF21B is regulated through TRIM3 (Labonte et al, 2013), an E3-ligase that assembles with the cytoskeleton-associated-recycling or transport (CART) complex, involved in vesicular receptor recycling (Yan et al, 2005).…”