| 2002 |
TRAK2 (GRIF-1) was identified as a GABA-A receptor beta2 subunit-interacting protein; the interaction was demonstrated by yeast two-hybrid assay and co-immunoprecipitation from HEK293 cells and adult rat brain lysates, with the respective binding domains mapped. |
Yeast two-hybrid assay, co-immunoprecipitation from transfected HEK293 cells and native rat brain lysates |
The Journal of biological chemistry |
Medium |
12034717
|
| 2005 |
TRAK2 (GRIF-1) associates with kinesin heavy chains (KIF5A in brain, KIF5B in heart/HEK293 cells, KIF5C by direct interaction) and with mitochondria; the GRIF-1/KIF5C interaction domain was localized to GRIF-1 residues 124–283 by yeast two-hybrid and co-immunoprecipitation. |
Co-immunoprecipitation from native brain/heart tissue and transfected HEK293 cells, yeast two-hybrid interaction assays |
The Journal of biological chemistry |
High |
15644324
|
| 2006 |
The GRIF-1 binding site on KIF5C was mapped to the KIF5C non-motor (cargo-binding) domain; the interaction is direct as demonstrated by FRET between fluorescently tagged GRIF-1 (N-terminal) and KIF5C (C-terminal), and GRIF-1 can bind the intact tetrameric kinesin light-chain/kinesin heavy-chain complex. |
Yeast two-hybrid with truncation constructs, co-immunoprecipitation, FRET with fluorescently tagged constructs, confocal microscopy |
The Journal of biological chemistry |
High |
16835241
|
| 2006 |
TRAK2 (GRIF-1) binds to the K+ channel Kir2.1 (interaction mapped to GRIF-1 N-terminus and Kir2.1 C-terminus by yeast two-hybrid), increases surface expression of Kir2.1 channels in COS and HEK293 cells, and enhances Kir2.1-mediated Rb+ efflux, establishing TRAK2 as a trafficking factor for this channel. |
Functional yeast growth rescue screen, 86Rb+ efflux assay, quantitative surface immunolabeling and flow cytometry, co-immunoprecipitation from HEK293 lysates and brain lysate, yeast two-hybrid domain mapping |
The Journal of biological chemistry |
High |
16895905
|
| 2008 |
TRAK2 (GRIF-1) and the atypical GTPase Miro1 form a protein complex on neuronal mitochondria; Miro1 recruits GRIF-1 to mitochondria in a manner dependent on its first GTPase domain. Overexpression of Miro1 enhanced mitochondrial transport toward distal neuronal processes, while expression of a Grif-1/Miro1 binding fragment dramatically reduced mitochondrial transport into processes. |
Co-immunoprecipitation from mammalian brain, fluorescence imaging of hippocampal neurons, dominant-negative GTPase domain mutants, overexpression and competitive fragment experiments |
Molecular and cellular neurosciences |
High |
19103291
|
| 2012 |
TRAK2 participates in a Kinesin/Miro/TRAK2 complex in neurons; the armadillo-repeat protein Alex3 interacts with this complex in a Ca2+-dependent manner, modulating mitochondrial dynamics and trafficking. |
Co-immunoprecipitation, fluorescence imaging of neurons, Ca2+-dependent binding assay |
Nature communications |
Medium |
22569362
|
| 2017 |
TRAK2 knockdown increases cholesterol efflux to apolipoprotein A-I and HDL via increased ABCA1 mRNA and protein expression, and increases LXR binding at the ABCA1 promoter; the efflux increase is abolished in the absence of ABCA1, placing TRAK2 as a regulator of LXR-mediated ABCA1 transcription and an ABCA1-dependent cholesterol efflux pathway. |
siRNA knockdown in THP-1 macrophages and HepG2 liver cells, cholesterol efflux assay, RT-PCR and western blot for ABCA1, chromatin immunoprecipitation for LXR at ABCA1 promoter, ABCA1 rescue/abolishment experiment |
European heart journal |
Medium |
28655204
|
| 2020 |
Caspase-3-cleaved tau significantly decreases TRAK2 protein expression in hippocampal and cortical neurons and increases TRAK2 association with mitochondria (without affecting RhoT1/T2, syntaphilin, KIF5, or dynein expression/localization), correlating with reduced mitochondrial transport and bioenergetic deficits; this identifies TRAK2 downregulation/mislocalization as a mechanism linking tau pathology to mitochondrial transport failure. |
GFP-tau overexpression in primary hippocampal neurons and immortalized cortical neurons, western blot, co-immunoprecipitation of TRAK2 with mitochondria, live-cell mitochondrial tracking |
Frontiers in cellular neuroscience |
Medium |
32848607
|
| 2021 |
TRAK2 is a dual motor activating adaptor: it activates kinesin-1 for plus-end-directed microtubule transport AND functions as a dynein activating adaptor via a conserved coiled-coil motif for minus-end transport (LIS1-dependent). TRAK2 simultaneously binds both kinesin-1 and dynein-dynactin, forming an interdependent motor complex in which knockdown of either motor reduces transport initiation toward both microtubule ends. |
Single-molecule imaging of cell lysates on microtubules, co-immunoprecipitation, co-localization, siRNA knockdown of kinesin-1 and dynein-dynactin, coiled-coil domain mutagenesis |
Nature communications |
High |
34321481
|
| 2025 |
A 29 bp 3'UTR motif in TRAK2 mRNA promotes cell-size-dependent polarized targeting of TRAK2 mRNA to distal cell protrusions, which scales mitochondria distribution by defining the site of TRAK2-MIRO1 retrograde transport complex assembly; excision of this motif perturbs size-regulated transport and causes distal mitochondrial accumulation. |
3'UTR motif deletion (CRISPR/genome editing implied), live mRNA imaging, mitochondrial distribution quantification, TRAK2-MIRO1 complex localization assay |
bioRxivpreprint |
Medium |
bio_10.1101_2025.05.05.652164
|